Clinical Focus


  • Food Allergy
  • Asthma
  • Allergy and Immunology

Academic Appointments


Professional Education


  • Residency: California Pacific Medical Center Dept of Medicine (2008) CA
  • Board Certification: American Board of Internal Medicine, Allergy and Immunology (2014)
  • Fellowship: Boston Medical Center (2013) MA
  • Board Certification: American Board of Internal Medicine, Critical Care Medicine (2012)
  • Fellowship: Boston Medical Center (2011) MA
  • Board Certification: American Board of Internal Medicine, Pulmonary Disease (2010)
  • Medical Education: Drexel University College of Medicine (2004) PA

Clinical Trials


  • Clinical Study Using Biologics to Improve Multi OIT Outcomes Recruiting

    Food allergy (FA) is a serious public health concern that causes potentially-life threatening reactions in affected patients. The prevalence of food allergy in the United States (U.S.) has increased substantially and now affects 15 million patients:4-8% of children (6 million children, 30% with multiple food allergies) and about 9% of adults. This is a prospective Phase 2, single-center, multi-allergen OIT study in participants with proven allergies to 2 or 3 different foods in which one must be a peanut. The total of participants in the clinical study will be 110, ages 4 to 55 years with a history of multiple food allergies of 2 to 3 different foods including peanut. Allergy will be confirmed by FA-specific IgE levels and positive skin prick test (SPT). Enrolled participants must be positive during the Double-blind Placebo-controlled Food challenge (DBPCFC) at or before the 300 mg (444 mg cumulative) dosing level of FA proteins.

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  • Dupilumab and Milk OIT for the Treatment of Cow's Milk Allergy Recruiting

    This is a phase 2, multicenter, randomized, double-blind, parallel group, 2 arm study in approximately 40 subjects aged 4 to 50 years, inclusive, who are allergic to cow's milk. The primary objective is to assess whether dupilumab as an adjunct to milk oral immunotherapy (OIT) compared to placebo improves the safety of milk OIT and rates of desensitization, defined as an increase in the proportion of subjects who pass a double-blind placebo-controlled food challenge (DBPCFC) to at least 2040 mg cumulative milk protein at week 18.

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  • Food Allergy Registry at a Single Site Recruiting

    This is a registry of participants who are interested in being screened for clinical trials at a single site.

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  • Gastrointestinal STRING Test With Oral Immunotherapy Recruiting

    This STRING study will examine markers of esophageal inflammation using a minimally-invasive testing device, the esophageal string test (EST). The primary objective is to determine the effect of omalizumab (Xolair) and dupilumab (Dupixent) on markers of eosinophilic inflammation in the esophagus of subjects treated with omalizumab-facilitated mOIT(mult-allergen oral immunotherapy) and/or mOIT with concurrent dupilumab.

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  • Safety Study of Viaskin Peanut to Treat Peanut Allergy Recruiting

    This study evaluates the safety of Viaskin Peanut 250 mcg in the treatment of peanut allergy in children from 4 to 11 years of age. Subjects will receive either Viaskin Peanut 250 mcg or a placebo for a period of 6 months, after which all subjects will be receiving the active treatment up to a period of 3 years under active treatment.

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  • Systems Biology of Early Atopy Recruiting

    The goal of this study is to establish a birth cohort that collects prenatal and early life biosamples and environmental samples and rigorously phenotypes young children for food allergy and Atopic Dermatitis (AD) to identify prenatal and early life markers of high risk for food allergy and AD, as well as biological pathways (endotypes) that result in these conditions. Primary Objectives: - To study the role and interrelationships of established and novel clinical, environmental, biological, and genetic prenatal and early-life factors in the development of allergic diseases through age 3 years, with an emphasis on atopic dermatitis and food allergy - To apply systems biology to identify mechanisms and biomarkers underlying the development of food allergy, atopic dermatitis, and their endotypes - To collect, process, and assay or store environmental and biological samples for current and future use in the study of allergic disease development

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  • Understanding Allergies and Sensitizations in Healthy and Allergic Individuals Recruiting

    The purpose of this study is to strengthen our ability to accurately diagnose allergies and understand cellular, humoral, genetic components and physiological changes in allergic disease

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  • Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen OIT in Food Allergic Participants Not Recruiting

    This study is a multi-center, randomized, double-blind, placebo-controlled study in participants 1 to less than 56 years of age who are allergic to peanut and at least two other foods (including milk, egg, wheat, cashew, hazelnut, or walnut). While each participant may be allergic to more than two other foods, the primary endpoint/outcome in this study will only be assessed in peanut and two other foods for each participant. The primary objective of the study is to compare the ability to consume foods without dose-limiting symptoms during a double-blind placebo-controlled food challenge (DBPCFC), after treatment with either omalizumab or placebo for omalizumab.

    Stanford is currently not accepting patients for this trial.

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  • Remote Monitoring of Respiratory Health Not Recruiting

    Recently, interest in ways to monitor and care for patients remotely has significantly increased due to concerns for infection control as well as a way to increase access to regular clinic visits that may be limited for socioeconomic and geographic reasons. However, remote care can be limited by a lack of objective data to help guide clinical care. With respect to respiratory disease, caring for patients remotely may be enhanced by the ability of patients to monitor at home such things as vital signs, lung sounds, and lung function by spirometry. Enhanced methods to follow symptoms and track medication compliance may also be beneficial. These enhancements could improve care and quality of life both for persons with acute respiratory illnesses and those with chronic respiratory disease (such as asthma or COPD). The purpose of this study is to develop and study methods for patients to monitor their respiratory health at home and make that data available to medical providers to improve their care.

    Stanford is currently not accepting patients for this trial.

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All Publications


  • CD8+ T cell differentiation status correlates with the feasibility of sustained unresponsiveness following oral immunotherapy. Nature communications Kaushik, A., Dunham, D., Han, X., Do, E., Andorf, S., Gupta, S., Fernandes, A., Kost, L. E., Sindher, S. B., Yu, W., Tsai, M., Tibshirani, R., Boyd, S. D., Desai, M., Maecker, H. T., Galli, S. J., Chinthrajah, R. S., DeKruyff, R. H., Manohar, M., Nadeau, K. C. 2022; 13 (1): 6646

    Abstract

    While food allergy oral immunotherapy (OIT) can provide safe and effective desensitization (DS), the immune mechanisms underlying development of sustained unresponsiveness (SU) following a period of avoidance are largely unknown. Here, we compare high dimensional phenotypes of innate and adaptive immune cell subsets of participants in a previously reported, phase 2 randomized, controlled, peanut OIT trial who achieved SU vs. DS (no vs. with allergic reactions upon food challenge after a withdrawal period; n=21 vs. 30 respectively among total 120 intent-to-treat participants). Lower frequencies of naive CD8+ T cells and terminally differentiated CD57+CD8+ T cell subsets at baseline (pre-OIT) are associated with SU. Frequency of naive CD8+ T cells shows a significant positive correlation with peanut-specific and Ara h 2-specific IgE levels at baseline. Higher frequencies of IL-4+ and IFNgamma+ CD4+ T cells post-OIT are negatively correlated with SU. Our findings provide evidence that an immune signature consisting of certain CD8+ T cell subset frequencies is potentially predictive of SU following OIT.

    View details for DOI 10.1038/s41467-022-34222-8

    View details for PubMedID 36333296

  • Comorbidity defines risk of asthmatics for COVID-19 hospitalization: a global perspective. The Journal of allergy and clinical immunology Skevaki, C., Chinthrajah, R. S., Fomina, D., Rohde, G., Cao, S., He, Z., Serdotetskova, S., Seidemann, C., Grunewaldt, A., Vengadeswaran, A., Xie, M., Karsonova, A., Karaulov, A., Nadeau, K. C., Chung, H., Renz, H. 2022

    Abstract

    BACKGROUND: The global epidemiology of asthma among COVID-19 patients presents striking geographic differences defining high and low [asthma and COVID-19] co-occurrence prevalence zones.OBJECTIVE: We aimed to compare asthma prevalence among hospitalized COVID-19 patients in major global hubs across the world with the application of common inclusion criteria and definitions.METHODS: We built a network of six academic hospitals in Stanford (Stanford University)/USA, Frankfurt (Goethe University), Giessen (Justus Liebig University) and Marburg (Philipps University)/Germany, and Moscow (Clinical Hospital 52 in collaboration with Sechenov University)/Russia. We collected clinical and laboratory data for patients hospitalized due to COVID-19.RESULTS: Asthmatics were overrepresented among hospitalized COVID-19 patients in Stanford and underrepresented in Moscow and Germany as compared to the prevalence among adults in the local community. Asthma prevalence was similar among ICU and hospital non-ICU patients, which implied that the risk for developing severe COVID-19 was not higher among asthmatics. The number of males and comorbidities was higher among COVID-19 patients in the Stanford cohort, and the most frequent comorbidities among these asthma patients were other chronic inflammatory airway disorders such as chronic obstructive pulmonary disease (COPD).CONCLUSION: Observed disparity in COVID-19-associated risk among asthmatics across countries and continents is connected to varying prevalence of underlying comorbidities, particularly COPD.CLINICAL IMPLICATION: Public health policies in the future will need to consider comorbidities with an emphasis on COPD for prioritization of vaccination and preemptive treatment.

    View details for DOI 10.1016/j.jaci.2022.09.039

    View details for PubMedID 36336123

  • The rationale for development of ligelizumab in food allergy. The World Allergy Organization journal Wood, R. A., Chinthrajah, R. S., Eggel, A., Bottoli, I., Gautier, A., Woisetschlaeger, M., Tassinari, P., Altman, P. 2022; 15 (9): 100690

    Abstract

    Food allergy (FA) is a growing healthcare problem worldwide and the rising prevalence in many countries can be attributed to lifestyle, environmental, and nutritional changes. Immunoglobulin E (IgE)-mediated FA is the most common form of FA affecting approximately 3%-10% of adults and 8% of children across the globe. Food allergen-induced immediate hypersensitivity reactions mediated by IgE and high-affinity IgE receptor (FcεRI) complexes on mast cells and basophils are a major hallmark of the disease. FA can affect several aspects of health-related quality of life and impose a substantial financial burden on patients and healthcare systems. Although currently there is one United States Food and Drug Administration (FDA) and European Medicines Agency (EMA)-approved treatment for peanut allergy (Palforzia), the main treatment approaches are based on allergen avoidance and symptom management. Thus, there is an urgent need for more effective and ideally disease-modifying strategies. Given the crucial role of IgE in FA, anti-IgE monoclonal antibodies are considered promising therapeutic agents. Talizumab was the first humanized anti-IgE antibody to demonstrate substantial protection against allergic reactions from accidental peanut exposure by substantially increasing the peanut reactivity threshold on oral food challenge. However, development of talizumab was discontinued and further trials were performed using omalizumab. In double-blind, Phase 2, placebo-controlled trials in patients with multi-FAs, sustained dosing with omalizumab, or omalizumab in combination with oral immunotherapy, enabled rapid desensitization to multiple trigger foods. In this review, we describe the development of ligelizumab (a derivative of talizumab), a next generation, humanized monoclonal anti-IgE antibody, its existing clinical evidence, and its potential in the management of FA. When compared with omalizumab, ligelizumab binds with ∼88-fold higher affinity for human IgE and recognizes a different epitope that substantially overlaps with the binding site of FcεRI. These properties translate into a high potency to block IgE/FcεRI signaling in both in vitro and in vivo studies. Given its efficient suppression of IgE levels, good safety and pharmacokinetic/pharmacodynamic profile, ligelizumab clearly warrants further studies for the potential management of FA.

    View details for DOI 10.1016/j.waojou.2022.100690

    View details for PubMedID 36185545

    View details for PubMedCentralID PMC9483652

  • Reply. The Journal of allergy and clinical immunology Chinthrajah, R. S., Togias, A., Wood, R. A. 2022

    View details for DOI 10.1016/j.jaci.2022.07.013

    View details for PubMedID 36050127

  • Treatment for Food Allergy: Current Status and Unmet Needs. The Journal of allergy and clinical immunology Dantzer, J. A., Kim, E. H., Chinthrajah, R. S., Wood, R. A. 2022

    Abstract

    The treatment of food allergy (FA) has traditionally relied on avoidance of the offending food(s) and use of emergency medications in the event of accidental exposures. However, this longstanding paradigm is beginning to shift, as a variety of treatment approaches have been and are being developed. In this manuscript, we seek to provide an overview of the past, present, and future landscape of interventional clinical trials for the treatment of FA. We focus on specific issues related to participant characteristics, protocol design, and study endpoints in the key clinical trials in the literature and examine how differences between studies may impact the clinical significance of the study results. We then provide recommendations for the optimization of future trial designs and focus on specific unmet needs in this rapidly evolving field.

    View details for DOI 10.1016/j.jaci.2022.08.008

    View details for PubMedID 35998790

  • The Impact of COVID-19 on a national sample of US Adults with Food Allergy. The journal of allergy and clinical immunology. In practice Warren, C., Sherr, J., Sindher, S., Nadeau, K. C., Casale, T. B., Ward, D., Gupta, R., Chinthrajah, R. S. 2022

    View details for DOI 10.1016/j.jaip.2022.07.036

    View details for PubMedID 35970447

  • Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study. EBioMedicine Ozonoff, A., Schaenman, J., Jayavelu, N. D., Milliren, C. E., Calfee, C. S., Cairns, C. B., Kraft, M., Baden, L. R., Shaw, A. C., Krammer, F., van Bakel, H., Esserman, D. A., Liu, S., Sesma, A. F., Simon, V., Hafler, D. A., Montgomery, R. R., Kleinstein, S. H., Levy, O., Bime, C., Haddad, E. K., Erle, D. J., Pulendran, B., Nadeau, K. C., Davis, M. M., Hough, C. L., Messer, W. B., Higuita, N. I., Metcalf, J. P., Atkinson, M. A., Brakenridge, S. C., Corry, D., Kheradmand, F., Ehrlich, L. I., Melamed, E., McComsey, G. A., Sekaly, R., Diray-Arce, J., Peters, B., Augustine, A. D., Reed, E. F., Altman, M. C., Becker, P. M., Rouphael, N. 2022; 83: 104208

    Abstract

    Better understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management.Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multivariable logistic regression was performed.The median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsupervised clustering of ordinal score over time revealed distinct disease course trajectories. Risk factors associated with prolonged hospitalization or death by day 28 included age ≥ 65 years (odds ratio [OR], 2.01; 95% CI 1.28-3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13-2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63- 4.80) or troponin (OR 1.89; 95% 1.03-3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61-2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96-5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17-2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) having at least one symptom consistent with PASC, most commonly dyspnea (56% among symptomatic patients). Female sex was the only associated risk factor for PASC.Integration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19.NIH.

    View details for DOI 10.1016/j.ebiom.2022.104208

    View details for PubMedID 35952496

  • Anti-nucleocapsid antibody levels and pulmonary comorbid conditions are linked to post-COVID-19 syndrome. JCI insight Jia, X., Cao, S., Lee, A. S., Manohar, M., Sindher, S. B., Ahuja, N., Artandi, M., Blish, C. A., Blomkalns, A. L., Chang, I., Collins, W. J., Desai, M., Din, H. N., Do, E., Fernandes, A., Geng, L. N., Rosenberg-Hasson, Y., Mahoney, M. R., Glascock, A. L., Chan, L. Y., Fong, S. Y., Phelps, M., Raeber, O., Purington, N., Röltgen, K., Rogers, A. J., Snow, T., Wang, T. T., Solis, D., Vaughan, L., Verghese, M., Maecker, H., Wittman, R., Puri, R., Kistler, A., Yang, S., Boyd, S. D., Pinsky, B. A., Chinthrajah, S., Nadeau, K. C. 2022; 7 (13)

    Abstract

    BACKGROUNDProlonged symptoms after SARS-CoV-2 infection are well documented. However, which factors influence development of long-term symptoms, how symptoms vary across ethnic groups, and whether long-term symptoms correlate with biomarkers are points that remain elusive.METHODSAdult SARS-CoV-2 reverse transcription PCR-positive (RT-PCR-positive) patients were recruited at Stanford from March 2020 to February 2021. Study participants were seen for in-person visits at diagnosis and every 1-3 months for up to 1 year after diagnosis; they completed symptom surveys and underwent blood draws and nasal swab collections at each visit.RESULTSOur cohort (n = 617) ranged from asymptomatic to critical COVID-19 infections. In total, 40% of participants reported at least 1 symptom associated with COVID-19 six months after diagnosis. Median time from diagnosis to first resolution of all symptoms was 44 days; median time from diagnosis to sustained symptom resolution with no recurring symptoms for 1 month or longer was 214 days. Anti-nucleocapsid IgG level in the first week after positive RT-PCR test and history of lung disease were associated with time to sustained symptom resolution. COVID-19 disease severity, ethnicity, age, sex, and remdesivir use did not affect time to sustained symptom resolution.CONCLUSIONWe found that all disease severities had a similar risk of developing post-COVID-19 syndrome in an ethnically diverse population. Comorbid lung disease and lower levels of initial IgG response to SARS-CoV-2 nucleocapsid antigen were associated with longer symptom duration.TRIAL REGISTRATIONClinicalTrials.gov, NCT04373148.FUNDINGNIH UL1TR003142 CTSA grant, NIH U54CA260517 grant, NIEHS R21 ES03304901, Sean N Parker Center for Allergy and Asthma Research at Stanford University, Chan Zuckerberg Biohub, Chan Zuckerberg Initiative, Sunshine Foundation, Crown Foundation, and Parker Foundation.

    View details for DOI 10.1172/jci.insight.156713

    View details for PubMedID 35801588

  • Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19. Cell reports. Medicine Feyaerts, D., Hédou, J., Gillard, J., Chen, H., Tsai, E. S., Peterson, L. S., Ando, K., Manohar, M., Do, E., Dhondalay, G. K., Fitzpatrick, J., Artandi, M., Chang, I., Snow, T. T., Chinthrajah, R. S., Warren, C. M., Wittman, R., Meyerowitz, J. G., Ganio, E. A., Stelzer, I. A., Han, X., Verdonk, F., Gaudillière, D. K., Mukherjee, N., Tsai, A. S., Rumer, K. K., Jacobsen, D. R., Bjornson-Hooper, Z. B., Jiang, S., Saavedra, S. F., Valdés Ferrer, S. I., Kelly, J. D., Furman, D., Aghaeepour, N., Angst, M. S., Boyd, S. D., Pinsky, B. A., Nolan, G. P., Nadeau, K. C., Gaudillière, B., McIlwain, D. R. 2022: 100680

    Abstract

    The biological determinants underlying the range of coronavirus 2019 (COVID-19) clinical manifestations are not fully understood. Here, over 1,400 plasma proteins and 2,600 single-cell immune features comprising cell phenotype, endogenous signaling activity, and signaling responses to inflammatory ligands are cross-sectionally assessed in peripheral blood from 97 patients with mild, moderate, and severe COVID-19 and 40 uninfected patients. Using an integrated computational approach to analyze the combined plasma and single-cell proteomic data, we identify and independently validate a multi-variate model classifying COVID-19 severity (multi-class area under the curve [AUC]training = 0.799, p = 4.2e-6; multi-class AUCvalidation = 0.773, p = 7.7e-6). Examination of informative model features reveals biological signatures of COVID-19 severity, including the dysregulation of JAK/STAT, MAPK/mTOR, and nuclear factor κB (NF-κB) immune signaling networks in addition to recapitulating known hallmarks of COVID-19. These results provide a set of early determinants of COVID-19 severity that may point to therapeutic targets for prevention and/or treatment of COVID-19 progression.

    View details for DOI 10.1016/j.xcrm.2022.100680

    View details for PubMedID 35839768

  • Food allergy, mechanisms, diagnosis and treatment: Innovation through a multi-targeted approach. Allergy Sindher, S. B., Long, A., Chin, A. R., Hy, A., Sampath, V., Nadeau, K. C., Chinthrajah, R. S. 2022

    Abstract

    The incidence of food allergy (FA) has continued to rise over the last several decades, posing significant burdens on health and quality of life. Significant strides into the advancement of FA diagnosis, prevention, and treatment have been made in recent years. In an effort to lower reliance on resource-intensive food challenges, the field has continued work toward the development of highly sensitive and specific assays capable of high-throughput analysis to assist in the diagnosis FA. In looking toward early infancy as a critical period in the development of allergy or acquisition of tolerance, evidence has increasingly suggested that early intervention via the early introduction of food allergens and maintenance of skin barrier function may decrease the risk of FA. As such, largescale investigations are underway evaluating infant feeding and the impact of emollient and steroid use in infants with dry skin for the prevention of allergy. On the other end of the spectrum, the past few years have been witness to an explosive increase in clinical trials of novel and innovative therapeutic strategies aimed at the treatment of FA in those whom the disease has already manifested. A milestone in the field, 2020 marked the approval of the first drug, oral peanut allergen, for the indication of peanut allergy. With a foundation of promising data supporting the safety and efficacy of single- and multi-allergen oral immunotherapy, current efforts have turned toward the use of probiotics, biologic agents, and modified allergens to optimize and improve upon existing paradigms. Through these advancements, the field hopes to gain footing in the ongoing battle against FA.

    View details for DOI 10.1111/all.15418

    View details for PubMedID 35730331

  • Current insights: a systemic review of therapeutic options for peanut allergy. Current opinion in allergy and clinical immunology O'Rourke, E., Tang, H., Chin, A., Long, A., Sindher, S., Chinthrajah, R. S. 2022; 22 (3): 188-193

    Abstract

    With increasing prevalence of peanut allergy (PA) globally and the greater risk of potential reactions occurring due to the leading role of nuts in food products, PA has become a significant public health concern over the past decade, affecting up to 5 million of the US adult population. This review details updates and advances in prevalence, diagnosis, and immunotherapies that have occurred over the past year.Therapeutic and diagnostic advances remain at the forefront of research and have continued to push the food allergy (FA) field forward to provide a promising role in the detection and treatment of PA. The FA field has researched significant advances in peanut immunotherapy, biomarker diagnosis, and quality of life (QoL) improvement.Given the burden and consequences for individuals with PA, these advances delivered in clinical practice can significantly improve the QoL of individuals with PA and their caregivers. Ongoing studies will continue to investigate long-term outcome measures of desensitisation and effective management plans tailored to the families' needs.

    View details for DOI 10.1097/ACI.0000000000000824

    View details for PubMedID 35660711

  • Updated threshold dose-distribution data for sesame. Allergy Turner, P. J., Gretzinger, M., Patel, N., Brough, H., Chinthrajah, R. S., Ebisawa, M., Elizur, A., Koplin, J. J., Peters, R. L., Purington, N., Nowak-Wegrzyn, A., Saf, S., Sampson, H. A., Westerhout, J., Blom, W. M., Baumert, J. L., Houben, G. F., Remington, B. C. 2022

    View details for DOI 10.1111/all.15364

    View details for PubMedID 35531634

  • Providing a safe nest for improved healthcare outcomes in pregnant women with asthma. The journal of allergy and clinical immunology. In practice Sindher, S. B., Fast, K., Nadeau, K. C., Chinthrajah, R. S. 2022

    Abstract

    There is a large unmet disease burden arising from asthma in pregnancy. Pregnant women affected by moderate to severe asthma have an increased risk of adverse perinatal outcomes. This can be worsened by social determinants of health (SDOH), which are social and environmental conditions that impact health and quality of life. Here we present the case of a medically complex pregnant woman with worsening asthma and challenges in optimizing positive outcomes for both mother and baby during the perinatal period. Her case captures several elements of SDOH that affect health outcomes most notably in nonwhite patients, including chronic exposure to air pollution contributing to asthma severity and reduced access to health care specialists.

    View details for DOI 10.1016/j.jaip.2022.03.004

    View details for PubMedID 35306179

  • Early Introduction of Multi-Allergen Mixture for Prevention of Food Allergy: Pilot Study. Nutrients Quake, A. Z., Liu, T. A., D'Souza, R., Jackson, K. G., Woch, M., Tetteh, A., Sampath, V., Nadeau, K. C., Sindher, S., Chinthrajah, R. S., Cao, S. 2022; 14 (4)

    Abstract

    The incidence and prevalence of food allergy (FA) is increasing. While several studies have established the safety and efficacy of early introduction of single allergens in infants for the prevention of FA, the exact dose, frequency, and number of allergens that can be safely introduced to infants, particularly in those at high or low risk of atopy, are still unclear. This 1-year pilot study evaluated the safety of the early introduction of single foods (milk, egg, or peanut) vs. two foods (milk/egg, egg/peanut, milk/peanut) vs. multiple foods (milk/egg/peanut/cashew/almond/shrimp/walnut/wheat/salmon/hazelnut at low, medium, or high doses) vs. no early introduction in 180 infants between 4-6 months of age. At the end of the study, they were evaluated for plasma biomarkers associated with food reactivity via standardized blood tests. Two to four years after the start of the study, participants were evaluated by standardized food challenges. The serving sizes for the single, double, and low dose mixtures were 300 mg total protein per day. The serving sizes for the medium and high dose mixtures were 900 mg and 3000 mg total protein, respectively. Equal parts of each protein were used for double or mixture foods. All infants were breastfed until at least six months of age. The results demonstrate that infants at either high or low risk for atopy were able to tolerate the early introduction of multiple allergenic foods with no increases in any safety issues, including eczema, FA, or food protein induced enterocolitis. The mixtures of foods at either low, medium, or high doses demonstrated trends for improvement in food challenge reactivity and plasma biomarkers compared to single and double food introductions. The results of this study suggest that the early introduction of foods, particularly simultaneous mixtures of many allergenic foods, may be safe and efficacious for preventing FA and can occur safely. These results need to be confirmed by larger randomized controlled studies.

    View details for DOI 10.3390/nu14040737

    View details for PubMedID 35215387

  • Dose-related allergic adverse events during multi-food oral immunotherapy Gajare, P., Cao, S., Anderson, B., Lloret, M., Zedeck, S., Kost, L., Nadeau, K., Chinthrajah, S., Sindher, S., Long, A. MOSBY-ELSEVIER. 2022: AB34
  • Feasibility of Virtual Reality Technology to Improve Experience During Pediatric Oral Food Challenge Collins, W., Adlou, B., Rodriguez, A., Albarran, M., O'Neal, E., Weiss, T., Hsu, K., Sindher, S., Bailenson, J., Caruso, T., Chinthrajah, S. MOSBY-ELSEVIER. 2022: AB108
  • Addressing Food Insecurity and Improving Food Allergy Management among Pediatric Patient/Caregiver Dyads During the COVID Pandemic Albarran, M., Warren, C., Chinthrajah, S., Martinez, E., Casareno, L., Rodriguez, A., Brown, E., Hampton, Q., Martinez, K., Kost, L. MOSBY-ELSEVIER. 2022: AB158
  • Updating the CoFAR Grading Scale for Systemic Allergic Reactions in Food Allergy Chinthrajah, S., Jones, S., Kim, E., Sicherer, S., Shreffler, W., Lanser, B., Atri, N., Babineau, D., Adelman, D., Iqbal, A., Limb, S., Spergel, A., Togias, A., Wood, R. MOSBY-ELSEVIER. 2022: AB107
  • Self-reported food allergy-associated anxiety during oral immunotherapy declines with time Jiang, S., Cao, S., Collins, W., Fast, K., Hampton, Q., Landes, G., Martinez, K., Tang, H., Sindher, S., Chinthrajah, S. MOSBY-ELSEVIER. 2022: AB140
  • SARS-CoV-2 and Perceived Physical, Mental and Social Health in Northern California Fast, K., Lee, A., Hampton, Q., Chinthrajah, S., Sindher, S., Jia, X., Collins, W., Nadeau, K., Cao, S. MOSBY-ELSEVIER. 2022: AB46
  • Using Nevisense Go to Identify Skin Epithelial Barrier Defect Lewis, S., Adlou, B., Kost, L., Nadeau, K., Chinthrajah, S., Long, A., Fast, K., Sindher, S. MOSBY-ELSEVIER. 2022: AB6
  • Climate Change and Global Health: A Call to more Research and more Action. Allergy Agache, I., Sampath, V., Aguilera, J., Akdis, C., Akdis, M., Barry, M., Bouagnon, A., Chinthrajah, S., Collins, W., Dulitzki, C., Erny, B., Gomez, J., Goshua, A., Jutel, M., Kizer, K. W., Kline, O., LaBeaud, A. D., Pali-Scholl, I., Perrett, K. P., Peters, R. L., Plaza, M. P., Prunicki, M., Sack, T., Salas, R. N., Sindher, S. B., Sokolow, S. H., Thiel, C., Veidis, E., Wray, B. D., Traidl-Hoffmann, C., Witt, C., Nadeau, K. C. 1800

    Abstract

    There is increasing understanding, globally, that climate change and increased pollution will have a profound and mostly harmful effect on human health. This review brings together international experts to describe both the direct (such as heat waves) and indirect (such as vector-borne disease incidence) health impacts of climate change. These impacts vary depending on vulnerability (i.e., existing diseases) and the international, economic, political and environmental context. This unique review also expands on these issues to address a third category of potential longer-term impacts on global health: famine, population dislocation, and environmental justice and education. This scholarly resource explores these issues fully, linking them to global health in urban and rural settings in developed and developing countries. The review finishes with a practical discussion of action that health professionals around the world in our field can yet take.

    View details for DOI 10.1111/all.15229

    View details for PubMedID 35073410

  • Efficacy and safety of oral immunotherapy in children aged 1-3 years with peanut allergy (the Immune Tolerance Network IMPACT trial): a randomised placebo-controlled study. Lancet (London, England) Jones, S. M., Kim, E. H., Nadeau, K. C., Nowak-Wegrzyn, A., Wood, R. A., Sampson, H. A., Scurlock, A. M., Chinthrajah, S., Wang, J., Pesek, R. D., Sindher, S. B., Kulis, M., Johnson, J., Spain, K., Babineau, D. C., Chin, H., Laurienzo-Panza, J., Yan, R., Larson, D., Qin, T., Whitehouse, D., Sever, M. L., Sanda, S., Plaut, M., Wheatley, L. M., Burks, A. W., Immune Tolerance Network 1800; 399 (10322): 359-371

    Abstract

    BACKGROUND: For young children with peanut allergy, dietary avoidance is the current standard of care. We aimed to assess whether peanut oral immunotherapy can induce desensitisation (an increased allergic reaction threshold while on therapy) or remission (a state of non-responsiveness after discontinuation of immunotherapy) in this population.METHODS: We did a randomised, double-blind, placebo-controlled study in five US academic medical centres. Eligible participants were children aged 12 to younger than 48 months who were reactive to 500 mg or less of peanut protein during a double-blind, placebo-controlled food challenge (DBPCFC). Participants were randomly assigned by use of a computer, in a 2:1 allocation ratio, to receive peanut oral immunotherapy or placebo for 134 weeks (2000 mg peanut protein per day) followed by 26 weeks of avoidance, with participants and study staff and investigators masked to group treatment assignment. The primary outcome was desensitisation at the end of treatment (week 134), and remission after avoidance (week 160), as the key secondary outcome, were assessed by DBPCFC to 5000 mg in the intention-to-treat population. Safety and immunological parameters were assessed in the same population. This trial is registered on ClinicalTrials.gov, NCT03345160.FINDINGS: Between Aug 13, 2013, and Oct 1, 2015, 146 children, with a median age of 39·3 months (IQR 30·8-44·7), were randomly assigned to receive peanut oral immunotherapy (96 participants) or placebo (50 participants). At week 134, 68 (71%, 95% CI 61-80) of 96 participants who received peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 who received placebo met the primary outcome of desensitisation (risk difference [RD] 69%, 95% CI 59-79; p<0·0001). The median cumulative tolerated dose during the week 134 DBPCFC was 5005 mg (IQR 3755-5005) for peanut oral immunotherapy versus 5 mg (0-105) for placebo (p<0·0001). After avoidance, 20 (21%, 95% CI 13-30) of 96 participants receiving peanut oral immunotherapy compared with one (2%, 0·05-11) of 50 receiving placebo met remission criteria (RD 19%, 95% CI 10-28; p=0·0021). The median cumulative tolerated dose during the week 160 DBPCFC was 755 mg (IQR 0-2755) for peanut oral immunotherapy and 0 mg (0-55) for placebo (p<0·0001). A significant proportion of participants receiving peanut oral immunotherapy who passed the 5000 mg DBPCFC at week 134 could no longer tolerate 5000 mg at week 160 (p<0·001). The participant receiving placebo who was desensitised at week 134 also achieved remission at week 160. Compared with placebo, peanut oral immunotherapy decreased peanut-specific and Ara h2-specific IgE, skin prick test, and basophil activation, and increased peanut-specific and Ara h2-specific IgG4 at weeks 134 and 160. By use of multivariable regression analysis of participants receiving peanut oral immunotherapy, younger age and lower baseline peanut-specific IgE was predictive of remission. Most participants (98% with peanut oral immunotherapy vs 80% with placebo) had at least one oral immunotherapy dosing reaction, predominantly mild to moderate and occurring more frequently in participants receiving peanut oral immunotherapy. 35 oral immunotherapy dosing events with moderate symptoms were treated with epinephrine in 21 participants receiving peanut oral immunotherapy.INTERPRETATION: In children with a peanut allergy, initiation of peanut oral immunotherapy before age 4 years was associated with an increase in both desensitisation and remission. Development of remission correlated with immunological biomarkers. The outcomes suggest a window of opportunity at a young age for intervention to induce remission of peanut allergy.FUNDING: National Institute of Allergy and Infectious Disease, Immune Tolerance Network.

    View details for DOI 10.1016/S0140-6736(21)02390-4

    View details for PubMedID 35065784

  • Durability of immune responses to the BNT162b2 mRNA vaccine MED Suthar, M. S., Arunachalam, P. S., Hu, M., Reis, N., Trisal, M., Raeber, O., Chinthrajah, S., Davis-Gardner, M. E., Manning, K., Mudvari, P., Boritz, E., Godbole, S., Henry, A. R., Douek, D. C., Halfmann, P., Kawaoka, Y., Boyd, S. D., Davis, M. M., Zarnitsyna, V. I., Nadeau, K., Pulendran, B. 2022; 3 (1): 25-27
  • Durability of immune responses to the BNT162b2 mRNA vaccine. Med (New York, N.Y.) Suthar, M. S., Arunachalam, P. S., Hu, M., Reis, N., Trisal, M., Raeber, O., Chinthrajah, S., Davis-Gardner, M. E., Manning, K., Mudvari, P., Boritz, E., Godbole, S., Henry, A. R., Douek, D. C., Halfmann, P., Kawaoka, Y., Boyd, S. D., Davis, M. M., Zarnitsyna, V. I., Nadeau, K., Pulendran, B. 2022; 3 (1): 25-27

    Abstract

    Antibody responses to the Pfizer-BioNTech mRNA vaccine waned substantially 6 months after the second vaccination.

    View details for DOI 10.1016/j.medj.2021.12.005

    View details for PubMedID 35590141

  • Updating the CoFAR Grading Scale for Systemic Allergic Reactions in Food Allergy. The Journal of allergy and clinical immunology Chinthrajah, R. S., Jones, S. M., Kim, E. H., Sicherer, S. H., Shreffler, W., Lanser, B. J., Atri, N., Babineau, D. C., Adelman, D. C., Iqbal, A., Limb, S. L., Rudman Spergel, A. K., Togias, A., Wood, R. A. 2022

    Abstract

    Immunotherapy is promising as an efficacious treatment for food allergy. Other food allergy treatments are also under development. However, adverse allergic events (AE) during treatment, as well as during oral food challenges (OFC) are common and reporting is not standardized.A more nuanced grading scale is needed to create a comprehensive and universal system to categorize AEs and their severity for food allergy clinical trials.Starting with the 2012 Consortium for Food Allergy Research (CoFAR) Grading Scale and the World Allergy Organization (WAO) Grading System, we developed the CoFAR Grading Scale for Systemic Allergic Reactions, Version 3.0, in collaboration with industry partners with expert opinion.The revised CoFAR Grading Scale for Systemic Allergic Reactions has five levels of increasing severity, ranging from generalized urticaria, localized angioedema, rhinitis, and abdominal pain (Grade 1) to death (Grade 5). Systemic reactions are further categorized within each grade by relevant organ system. Mild, single-system reactions are differentiated from mild, multi-system reactions. Lower respiratory symptoms are graded based on response to therapy; those that are refractory to standard treatment (e.g., requiring >3 doses of IM epinephrine, continuous IV epinephrine infusion, continuous albuterol nebulization) and respiratory compromise requiring mechanical ventilation are classified as Grade 4, life-threatening reactions.Universal and consistent use of the revised CoFAR Grading Scale beyond the CoFAR centers would allow for better data aggregation and safety comparisons in clinical trials for food allergy.

    View details for DOI 10.1016/j.jaci.2021.12.789

    View details for PubMedID 35026206

  • Gastrointestinal γδ T cells reveal differentially expressed transcripts and enriched pathways during peanut oral immunotherapy. Allergy Zhang, W., Krishna Dhondalay, G., Liu, T. A., Kaushik, A., Hoh, R., Kwok, S., Kambham, N., Fernandez-Becker, N. Q., Andorf, S., Desai, M., Galli, S. J., Boyd, S. D., Nadeau, K. C., Manohar, M., DeKruyff, R. H., Chinthrajah, R. S. 2022

    View details for DOI 10.1111/all.15250

    View details for PubMedID 35143054

  • Efficacy and safety of oral immunotherapy in children aged 1-3 years with peanut allergy (the Immune Tolerance Network IMPACT trial): a randomised placebo-controlled study LANCET Jones, S. M., Kim, E. H., Nadeau, K. C., Nowak-Wegrzyn, A., Wood, R. A., Sampson, H. A., Scurlock, A. M., Chinthrajah, S., Wang, J., Pesek, R. D., Sindher, S. B., Kulis, M., Johnson, J., Spain, K., Babineau, D. C., Chin, H., Laurienzo-Panza, J., Yan, R., Larson, D., Qin, T., Whitehouse, D., Sever, M. L., Sanda, S., Plaut, M., Wheatley, L. M., Burks, A., Immune Tolerance Network 2022; 399 (10322): 359-371
  • A phase 2, randomized multi oral immunotherapy with Omalizumab 'real life' study. Allergy Sindher, S. B., Kumar, D., Cao, S., Purington, N., Long, A., Sampath, V., Zedeck, S. S., Woch, M. A., Garcia-Lloret, M., Chinthrajah, R. S. 2022

    Abstract

    Oral immunotherapy (OIT) is frequently discontinued due to adverse events (AEs) and current data suggests that lowering OIT doses can minimize severity and frequency of AEs. However, the minimum daily dose that can enable desensitization and induce immune responses in multi-food OIT (mOIT) is unknown.Participants aged 2-25 years with multi-food allergies were pretreated with fixed dose omalizumab (150 mg, 3 doses, every 4 weeks), and randomized 1:1 to receive mOIT to a total maintenance dose of either 300 or 1200 mg total protein, (total dose includes at least two and up to a max of five allergens) and then transitioned to real food protein equivalents after 18 weeks of treatment. The primary endpoint was the proportion of subjects with increases in IgG4/IgE ratio of at least 2 allergens by ≥25% from baseline after 18 weeks of therapy. The primary efficacy and safety analyses was done in the intention-to-treat population.Sixty participants were enrolled across two sites. Seventy percent of participants in both arms showed changes in sIgG4/sIgE ratio in at least 2 allergens with no difference between the treatment groups (OR (95% CI) =1.00 (0.29, 3.49)). Overall, there were no differences in AEs between the 300 and 1200 mg groups (19% vs. 17%, P = 0.69), respectively.Our data suggests that plasma marker changes are induced early, even at a total protein dose of 300 mg inclusive of multiple allergens when mOIT is combined with fixed dose omalizumab. Identification of optimal mOIT dosing with adjunct omalizumab is needed for the long-term success of OIT.

    View details for DOI 10.1111/all.15217

    View details for PubMedID 35014049

  • Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination. Cell Röltgen, K., Nielsen, S. C., Silva, O., Younes, S. F., Zaslavsky, M., Costales, C., Yang, F., Wirz, O. F., Solis, D., Hoh, R. A., Wang, A., Arunachalam, P. S., Colburg, D., Zhao, S., Haraguchi, E., Lee, A. S., Shah, M. M., Manohar, M., Chang, I., Gao, F., Mallajosyula, V., Li, C., Liu, J., Shoura, M. J., Sindher, S. B., Parsons, E., Dashdorj, N. J., Dashdorj, N. D., Monroe, R., Serrano, G. E., Beach, T. G., Chinthrajah, R. S., Charville, G. W., Wilbur, J. L., Wohlstadter, J. N., Davis, M. M., Pulendran, B., Troxell, M. L., Sigal, G. B., Natkunam, Y., Pinsky, B. A., Nadeau, K. C., Boyd, S. D. 2022

    Abstract

    During the SARS-CoV-2 pandemic, novel and traditional vaccine strategies have been deployed globally. We investigated whether antibodies stimulated by mRNA vaccination (BNT162b2), including third-dose boosting, differ from those generated by infection or adenoviral (ChAdOx1-S and Gam-COVID-Vac) or inactivated viral (BBIBP-CorV) vaccines. We analyzed human lymph nodes after infection or mRNA vaccination for correlates of serological differences. Antibody breadth against viral variants is lower after infection compared with all vaccines evaluated but improves over several months. Viral variant infection elicits variant-specific antibodies, but prior mRNA vaccination imprints serological responses toward Wuhan-Hu-1 rather than variant antigens. In contrast to disrupted germinal centers (GCs) in lymph nodes during infection, mRNA vaccination stimulates robust GCs containing vaccine mRNA and spike antigen up to 8 weeks postvaccination in some cases. SARS-CoV-2 antibody specificity, breadth, and maturation are affected by imprinting from exposure history and distinct histological and antigenic contexts in infection compared with vaccination.

    View details for DOI 10.1016/j.cell.2022.01.018

    View details for PubMedID 35148837

  • Oral Immunotherapy in Children: Clinical Considerations and Practical Management. Journal of asthma and allergy Anderson, B., Wong, L., Adlou, B., Long, A., Chinthrajah, R. S. 2021; 14: 1497-1510

    Abstract

    Oral immunotherapy (OIT) in pediatric patients provides an alternative option to the current standard of care in food allergy, which is allergen avoidance and reactive treatment. Because patients are exposed to one or more food allergens during treatment, OIT is associated with adverse events and can be a cumbersome process for children, their caregivers, and clinicians. However, there have been an overwhelming number of studies that show high efficacy in both single- and multi-allergen OIT, and that quality of life is greatly improved for both patients and their families after undergoing immunotherapy. This review discusses clinical considerations for OIT in pediatrics, including efficacy and safety, practical management, and future directions of treatment.

    View details for DOI 10.2147/JAA.S282696

    View details for PubMedID 34934327

    View details for PubMedCentralID PMC8684389

  • Food allergy across the globe. The Journal of allergy and clinical immunology Sampath, V., Abrams, E. M., Adlou, B., Akdis, C., Akdis, M., Brough, H. A., Chan, S., Chatchatee, P., Chinthrajah, R. S., Cocco, R. R., Deschildre, A., Eigenmann, P., Galvan, C., Gupta, R., Hossny, E., Koplin, J. J., Lack, G., Levin, M., Shek, L. P., Makela, M., Mendoza-Hernandez, D., Muraro, A., Papadopoulous, N. G., Pawankar, R., Perrett, K. P., Roberts, G., Sackesen, C., Sampson, H., Tang, M. L., Togias, A., Venter, C., Warren, C. M., Wheatley, L. M., Wong, G. W., Beyer, K., Nadeau, K. C., Renz, H. 2021; 148 (6): 1347-1364

    Abstract

    The prevalence of food allergy (FA) is increasing in some areas of the globe, highlighting the need for better strategies for prevention, diagnosis, and therapy. In the last few decades, we have made great strides in understanding the causes and mechanisms underlying FAs, prompting guideline updates. Earlier guidelines recommended avoidance of common food allergens during pregnancy and lactation and delaying the introduction of allergenic foods in children aged between 1 and 3 years. Recent guidelines for allergy prevention recommend consumption of a healthy and diverse diet without eliminating or increasing the consumption of allergenic foods during pregnancy or breast-feeding. Early introduction of allergenic foods is recommended by most guidelines for allergy prevention after a period of exclusive breast-feedng (6 months [World Health Organization] or 4 months [European Academy of Allergy and Clinical Immunology]). New diagnostics for FA have been developed with varied availability of these tests in different countries. Finally, the first oral immunotherapy drug for FA was approved by the US Food and Drug Administration and European Medicines Agency in 2020. In this review, we will address the global prevalence of FA, our current understanding of the causes of FA, and the latest guidelines for preventing, diagnosing, and treating FA. We will alsodiscuss similarities and differences between FA guidelines.

    View details for DOI 10.1016/j.jaci.2021.10.018

    View details for PubMedID 34872649

  • Safety of Epicutaneous Immunotherapy in Peanut-Allergic Children: REALISE Randomized Clinical Trial Results. The journal of allergy and clinical immunology. In practice Pongracic, J. A., Gagnon, R., Sussman, G., Siri, D., Oriel, R. C., Brown-Whitehorn, T., Green, T. D., Campbell, D. E., Anvari, S., Berger, W. E., Bird, J. A., Chan, E. S., Cheema, A., Chinthrajah, S., Chong, H., Dowling, P. J., Fineman, S. M., Fleischer, D. M., Gonzalez-Reyes, E., Kim, E. H., Lanser, B. J., MacGinnitie, A., Mehta, H., Petroni, D., Rupp, N., Schneider, L. C., Scurlock, A. M., Sher, L. D., Shreffler, W. G., Sindher, S. B., Stillerman, A., Wood, R., Yang, W. H., Bois, T., Sampson, H. A., Begin, P. 2021

    Abstract

    BACKGROUND: Treatment options for peanut allergy are limited. In previous clinical trials, epicutaneous immunotherapy with a patch containing 250-mug peanut protein (Viaskin Peanut 250 mug [VP250]) was well tolerated and statistically superior to placebo in desensitizing peanut-allergic children.OBJECTIVE: To examine the safety of VP250 in children, using a study design approximating potential real-world use.METHODS: REALISE is a phase 3 multicenter study consisting of a 6-month, randomized, double-blind, placebo-controlled period followed by open-label active treatment. Children aged 4 to 11 years with physician diagnosis of peanut allergy received daily treatment with placebo (6 months) or VP250 (up to 36 months). Data from the 6-month, randomized, controlled phase of REALISE are reported.RESULTS: Three hundred ninety-three children were randomized 3:1 to receive VP250 (n=294) or placebo (n=99) for 6 months; 284 (72.3%) children had a history of peanut anaphylaxis. According to parent diary, all participants receiving VP250 and 83.8% receiving placebo reported at least 1 episode of local skin reaction, with frequency decreasing over time. Only 4 participants (1.4%) receiving VP250 discontinued due to adverse events. Epinephrine was administered for allergic reactions attributed to VP250 in 7 children (2.4%), of whom 5 remained in the study; none involved severe anaphylaxis. Overall adverse event rates were similar among participants with and without history of peanut anaphylaxis.CONCLUSIONS: In a study designed to mirror real-world use, VP250 was observed to be well tolerated in peanut-allergic children, consistent with previous phase 2b and 3 studies.

    View details for DOI 10.1016/j.jaip.2021.11.017

    View details for PubMedID 34848381

  • Direct comparison of antibody responses to four SARS-CoV-2 vaccines in Mongolia. Cell host & microbe Dashdorj, N. J., Wirz, O. F., Roltgen, K., Haraguchi, E., Buzzanco, A. S., Sibai, M., Wang, H., Miller, J. A., Solis, D., Sahoo, M. K., Arunachalam, P. S., Lee, A. S., Shah, M. M., Liu, J., Byambabaatar, S., Bat-Ulzii, P., Enkhbat, A., Batbold, E., Zulkhuu, D., Ochirsum, B., Khurelsukh, T., Dalantai, G., Burged, N., Baatarsuren, U., Ariungerel, N., Oidovsambuu, O., Bungert, A. S., Genden, Z., Yagaanbuyant, D., Mordorj, A., Pulendran, B., Chinthrajah, S., Nadeau, K. C., Jardetzky, T., Wilbur, J. L., Wohlstadter, J. N., Sigal, G. B., Pinsky, B. A., Boyd, S. D., Dashdorj, N. D. 2021

    Abstract

    Different SARS-CoV-2 vaccines are approved in various countries, but few direct comparisons of the antibody responses they stimulate have been reported. We collected plasma specimens in July 2021 from 196 Mongolian participants fully vaccinated with one of four COVID-19 vaccines: Pfizer/BioNTech, AstraZeneca, Sputnik V, and Sinopharm. Functional antibody testing with a panel of nine SARS-CoV-2 viral variant receptor binding domain (RBD) proteins revealed marked differences in vaccine responses, with low antibody levels and RBD-ACE2 blocking activity stimulated by the Sinopharm and Sputnik V vaccines in comparison to the AstraZeneca or Pfizer/BioNTech vaccines. The Alpha variant caused 97% of infections in Mongolia in June and early July 2021. Individuals who recover from SARS-CoV-2 infection after vaccination achieve high antibody titers in most cases. These data suggest that public health interventions such as vaccine boosting, potentially with more potent vaccine types, may be needed to control COVID-19 in Mongolia and worldwide.

    View details for DOI 10.1016/j.chom.2021.11.004

    View details for PubMedID 34861167

  • Shrimp-Allergic Patients in a Multi-Food Oral Immunotherapy Trial. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology Nguyen, D. I., Sindher, S. B., Chinthrajah, R. S., Nadeau, K., Davis, C. M. 2021

    Abstract

    Shellfish allergy is one of the most common food allergies in the United States, accounting for approximately 25% of adulthood and 20% of childhood food allergies (FA).1,2 Of the different types of shellfish, shrimp is a common culprit of food allergy. The prevalence of shellfish allergy in children is substantial at 1.3% and may result in a greater prevalence in the adult population (3%) given that shellfish allergies have a low rate of spontaneous resolution.2,3.

    View details for DOI 10.1111/pai.13679

    View details for PubMedID 34655480

  • New-onset IgG autoantibodies in hospitalized patients with COVID-19. Nature communications Chang, S. E., Feng, A., Meng, W., Apostolidis, S. A., Mack, E., Artandi, M., Barman, L., Bennett, K., Chakraborty, S., Chang, I., Cheung, P., Chinthrajah, S., Dhingra, S., Do, E., Finck, A., Gaano, A., GeSSner, R., Giannini, H. M., Gonzalez, J., Greib, S., Gundisch, M., Hsu, A. R., Kuo, A., Manohar, M., Mao, R., Neeli, I., Neubauer, A., Oniyide, O., Powell, A. E., Puri, R., Renz, H., Schapiro, J., Weidenbacher, P. A., Wittman, R., Ahuja, N., Chung, H., Jagannathan, P., James, J. A., Kim, P. S., Meyer, N. J., Nadeau, K. C., Radic, M., Robinson, W. H., Singh, U., Wang, T. T., Wherry, E. J., Skevaki, C., Luning Prak, E. T., Utz, P. J. 2021; 12 (1): 5417

    Abstract

    COVID-19 is associated with a wide range of clinical manifestations, including autoimmune features and autoantibody production. Here we develop three protein arrays to measure IgG autoantibodies associated with connective tissue diseases, anti-cytokine antibodies, and anti-viral antibody responses in serum from 147 hospitalized COVID-19 patients. Autoantibodies are identified in approximately 50% of patients but in less than 15% of healthy controls. When present, autoantibodies largely target autoantigens associated with rare disorders such as myositis, systemic sclerosis and overlap syndromes. A subset of autoantibodies targeting traditional autoantigens or cytokines develop de novo following SARS-CoV-2 infection. Autoantibodies track with longitudinal development of IgG antibodies recognizing SARS-CoV-2 structural proteins and a subset of non-structural proteins, but not proteins from influenza, seasonal coronaviruses or other pathogenic viruses. We conclude that SARS-CoV-2 causes development of new-onset IgG autoantibodies in a significant proportion of hospitalized COVID-19 patients and are positively correlated with immune responses to SARS-CoV-2 proteins.

    View details for DOI 10.1038/s41467-021-25509-3

    View details for PubMedID 34521836

  • Assessment of Allergic and Anaphylactic Reactions to mRNA COVID-19 Vaccines With Confirmatory Testing in a US Regional Health System. JAMA network open Warren, C. M., Snow, T. T., Lee, A. S., Shah, M. M., Heider, A., Blomkalns, A., Betts, B., Buzzanco, A. S., Gonzalez, J., Chinthrajah, R. S., Do, E., Chang, I., Dunham, D., Lee, G., O'Hara, R., Park, H., Shamji, M. H., Schilling, L., Sindher, S. B., Sisodiya, D., Smith, E., Tsai, M., Galli, S. J., Akdis, C., Nadeau, K. C. 2021; 4 (9): e2125524

    Abstract

    Importance: As of May 2021, more than 32 million cases of COVID-19 have been confirmed in the United States, resulting in more than 615 000 deaths. Anaphylactic reactions associated with the Food and Drug Administration (FDA)-authorized mRNA COVID-19 vaccines have been reported.Objective: To characterize the immunologic mechanisms underlying allergic reactions to these vaccines.Design, Setting, and Participants: This case series included 22 patients with suspected allergic reactions to mRNA COVID-19 vaccines between December 18, 2020, and January 27, 2021, at a large regional health care network. Participants were individuals who received at least 1 of the following International Statistical Classification of Diseases and Related Health Problems, Tenth Revision anaphylaxis codes: T78.2XXA, T80.52XA, T78.2XXD, or E949.9, with documentation of COVID-19 vaccination. Suspected allergy cases were identified and invited for follow-up allergy testing.Exposures: FDA-authorized mRNA COVID-19 vaccines.Main Outcomes and Measures: Allergic reactions were graded using standard definitions, including Brighton criteria. Skin prick testing was conducted to polyethylene glycol (PEG) and polysorbate 80 (P80). Histamine (1 mg/mL) and filtered saline (negative control) were used for internal validation. Basophil activation testing after stimulation for 30 minutes at 37 °C was also conducted. Concentrations of immunoglobulin (Ig) G and IgE antibodies to PEG were obtained to determine possible mechanisms.Results: Of 22 patients (20 [91%] women; mean [SD] age, 40.9 [10.3] years; 15 [68%] with clinical allergy history), 17 (77%) met Brighton anaphylaxis criteria. All reactions fully resolved. Of patients who underwent skin prick tests, 0 of 11 tested positive to PEG, 0 of 11 tested positive to P80, and 1 of 10 (10%) tested positive to the same brand of mRNA vaccine used to vaccinate that individual. Among these same participants, 10 of 11 (91%) had positive basophil activation test results to PEG and 11 of 11 (100%) had positive basophil activation test results to their administered mRNA vaccine. No PEG IgE was detected; instead, PEG IgG was found in tested individuals who had an allergy to the vaccine.Conclusions and Relevance: Based on this case series, women and those with a history of allergic reactions appear at have an elevated risk of mRNA vaccine allergy. Immunological testing suggests non-IgE-mediated immune responses to PEG may be responsible in most individuals.

    View details for DOI 10.1001/jamanetworkopen.2021.25524

    View details for PubMedID 34533570

  • New-Onset IgG Autoantibodies in Hospitalized Patients with COVID-19 Chang, S., Feng, A., Meng, W., Apostolidis, S., Mack, E., Artandi, M., Barman, L., Bennett, K., Chakraborty, S., Chang, I., Cheung, P., Chinthrajah, S., Dhingra, S., Do, E., Finck, A., Gaano, A., Gessner, R., Giannini, H., Gonzalez, J., Greib, S., Gundisch, M., Hsu, A., Kuo, A., Manohar, M., Mao, R., Neeli, I., Neubauer, A., Oniyide, O., Powell, A., Puri, R., Renz, H., Schapiro, J., Weidenbacher, P., Wittman, R., Ahuja, N., Chung, H., Jagannathan, P., James, J., Kim, P., Meyer, N., Nadeau, K., Radic, M., Robinson, W., Singh, U., Wang, T., Wherry, J., Skevaki, C., Prak, E., Utz, P. WILEY. 2021: 3202-3205
  • Asthma phenotypes, associated comorbidities, and long-term symptoms in COVID-19. Allergy Eggert, L. E., He, Z., Collins, W., Lee, A. S., Dhondalay, G., Jiang, S. Y., Fitzpatrick, J., Snow, T. T., Pinsky, B. A., Artandi, M., Barman, L., Puri, R., Wittman, R., Ahuja, N., Blomkalns, A., O'Hara, R., Cao, S., Desai, M., Sindher, S. B., Nadeau, K., Chinthrajah, R. S. 2021

    Abstract

    BACKGROUND: It is unclear if asthma and its allergic phenotype are risk factors for hospitalization or severe disease from SARS-CoV-2.METHODS: All patients over 28 days oldtesting positive for SARS-CoV-2 between March 1 and September 30, 2020, were retrospectively identified and characterized through electronic analysis at Stanford. A sub-cohort was followed prospectively to evaluate long-term COVID-19 symptoms.RESULTS: 168,190 patients underwent SARS-CoV-2 testing, and 6,976 (4.15%) tested positive. In a multivariate analysis, asthma was not an independent risk factor for hospitalization (OR 1.12 [95% CI 0.86, 1.45], p=0.40). Among SARS-CoV-2 positive asthmatics, allergic asthma lowered the risk of hospitalization and had a protective effect compared to non-allergic asthma (OR 0.52 (0.28, 0.91), p=0.026); there was no association between baseline medication use as characterized by GINA and hospitalization risk. Patients with severe COVID-19 disease had lower eosinophil levels during hospitalization compared to patients with mild or asymptomatic disease, independent of asthma status (p=0.0014). In a patient sub-cohort followed longitudinally, asthmatics and non-asthmatics had similar time to resolution of COVID-19 symptoms, particularly lower respiratory symptoms.CONCLUSIONS: Asthma is not a risk factor for more severe COVID-19 disease. Allergic asthmatics were half as likely to be hospitalized with COVID-19 compared to non-allergic asthmatics. Lower levels of eosinophil counts (allergic biomarkers) were associated with a more severe COVID-19 disease trajectory. Recovery was similar among asthmatics and non-asthmatics with over 50% of patients reporting ongoing lower respiratory symptoms three months post-infection.

    View details for DOI 10.1111/all.14972

    View details for PubMedID 34080210

  • Improvement in health-related quality of life in food-allergic patients: a meta-analysis. The journal of allergy and clinical immunology. In practice Cao, S., Borro, M., Alonzi, S., Sindher, S., Nadeau, K., Chinthrajah, R. S. 2021

    Abstract

    BACKGROUND: Food allergy (FA) is a growing global problem and can affect patients' health related quality of life (HRQoL) due to increased anxiety as well as social and economic restrictions. Interventions such as oral food challenges (OFCs) and oral immunotherapy (OIT) have been shown to improve HRQoL, however, meta-analysis and systematic synthesis of these data are lacking.OBJECTIVE: The objective of this study was to systematically review and quantitatively synthesize potential benefits of interventions (OIT and OFC) for addressing FA to a variety of foods.METHODS: We conducted a systematic search through PubMed and Cochrane Medical Library databases and performed a meta-analysis focusing on studies assessing changes in HRQoL after OIT and/or OFCs in FA participants and caregivers from 2010 to July 2020. Random effects model and I2 statistics were used to assess the overall intervention effects and heterogeneity across studies.RESULTS: We included 13 publications in this meta-analysis (OIT=7, OFCs=6). The mean change of HRQoL scores after OIT and OFCs were -1.25 (P<0.001) and -0.78 (P=0.052), with significant I2 of 87% (P<0.001) and 90% (P<0.001), respectively. Five OIT studies found significant improvements in HRQoL in the OIT group compared to the placebo group with an overall standardized mean difference of -0.56 (P=0.007; I2=42%, P=0.099).CONCLUSION: This meta-analysis showed that in FA patients, both OIT and OFCs are associated with an improvement in HRQoL. Well-designed and long-term HRQoL studies are necessary to ascertain sustained benefits of OIT and OFCs.

    View details for DOI 10.1016/j.jaip.2021.05.020

    View details for PubMedID 34089927

  • Accurate and Reproducible Diagnosis of Peanut Allergy Using Epitope Mapping. Allergy Suarez-Farinas, M., Suprun, M., Kearney, P., Getts, R., Grishina, G., Hayward, C., Luta, D., Porter, A., Witmer, M., du Toit, G., Lack, G., Chinthrajah, R. S., Galli, S. J., Nadeau, K., Sampson, H. A. 2021

    Abstract

    BACKGROUND: Accurate diagnosis of peanut allergy is a significant clinical challenge. Here, a novel diagnostic blood test using the peanut Bead-Based Epitope Assay ("peanut BBEA") was developed utilizing the LEAP cohort and then validated using two independent cohorts.METHODS: The development of the peanut BBEA diagnostic test followed the National Academy of Medicine's established guidelines with discovery performed on 133 subjects from the non-interventional arm of the LEAP trial and an independent validation performed on 82 subjects from the CoFAR2 and 84 subjects from the POISED study. All samples were analyzed using the peanut BBEA methodology,which measures levels of IgE to two Ara h 2 sequential (linear) epitopes and compares their combination to a threshold pre-specified in the model development phase. When a patient has an inconclusive outcome by skin prick testing(or sIgE), IgE antibody levelsto this combination of two epitopes candistinguish whether the patient is "Allergic" or "Not Allergic." Diagnoses of peanut allergy in all subjects were confirmed by double-blind placebo-controlled food challenge and subjects' ages were 7-55 years.RESULTS: In the validation usingCoFAR2 and POISED cohorts, the peanut BBEA diagnostic test correctly diagnosed 93% of the subjects, with a sensitivity of 91%, specificity of 95%, a positive predictive value of 95% and negative predictive value of 91%.CONCLUSIONS: In validation of the peanut BBEA diagnostic test, the overall accuracy was found to be superior to existing diagnostic tests for peanut allergy including skin prick testing, peanut sIgE and peanut component sIgE testing.

    View details for DOI 10.1111/all.14905

    View details for PubMedID 33991353

  • Novel application of a discrete time-to-event model for randomized oral immunotherapy clinical trials with repeat food challenges. Statistics in medicine Purington, N., Andorf, S., Bunning, B., Chinthrajah, S., Nadeau, K., Desai, M. 2021

    Abstract

    The evaluation of double-blind, placebo-controlled food challenges (DBPCFC) generally focuses on a participant passing a challenge at a predetermined dose, and does not consider the dose of reaction for those who fail or are censored due to study discontinuation. Further, a number of food allergy trials have incorporated multiple DBPCFCs throughout the duration of the study in order to evaluate changes in reaction over time including sustained unresponsiveness from treatment. Outcomes arising from these trials are commonly modeled using Chi-squared or Fisher's exact tests at each time point. We propose applying time-to-event methodology to food allergy trials in order to exploit the inherent granularity of challenge outcomes that additionally accommodates repeated DBPCFCs. Specifically, we consider dose-to-failure for each study challenge and extend the cumulative tolerated dose across challenges to result in a dose-time axis. A discrete time-to-event framework is applied to the dose-time outcome to assess the efficacy of treatment across the entire study period. We illustrate ideas with data from the Peanut Oral Immunotherapy Study: Safety, Efficacy and Discovery (POISED) trial, conducted at Stanford University, which evaluated the efficacy of oral immunotherapy on desensitization and sustained unresponsiveness in peanut allergic children and adults. We demonstrate the advantages of time-to-event approaches for assessing the efficacy of treatment over time and incorporating information for those who failed or were lost to follow up. Further, we introduce a dose-time outcome that is interpretable to clinicians and allows for examination of such outcomes over time.

    View details for DOI 10.1002/sim.9019

    View details for PubMedID 33959986

  • Systems biological assessment of human immunity to BNT162b2 mRNA vaccination. Research square Arunachalam, P. S., Scott, M. K., Hagan, T., Li, C., Feng, Y., Wimmers, F., Grigoryan, L., Trisal, M., Edara, V. V., Lai, L., Chang, S. E., Feng, A., Dhingra, S., Shah, M., Lee, A. S., Chinthrajah, S., Sindher, T., Mallajosyula, V., Gao, F., Sigal, N., Kowli, S., Gupta, S., Pellegrini, K., Tharp, G., Maysel-Auslender, S., Bosinger, S., Maecker, H. T., Boyd, S. D., Davis, M. M., Utz, P. J., Suthar, M. S., Khatri, P., Nadeau, K. C., Pulendran, B. 2021

    Abstract

    The emergency use authorization of two COVID-19 mRNA vaccines in less than a year since the emergence of SARS-CoV-2, represents a landmark in vaccinology1,2. Yet, how mRNA vaccines stimulate the immune system to elicit protective immune responses is unknown. Here we used a systems biological approach to comprehensively profile the innate and adaptive immune responses in 56 healthy volunteers vaccinated with the Pfizer-BioNTech mRNA vaccine. Vaccination resulted in robust production of neutralizing antibodies (nAbs) against the parent strain and the variant of concern, B.1.351, but no induction of autoantibodies, and significant increases in antigen-specific polyfunctional CD4 and CD8 T cells after the second dose. The innate response induced within the first 2 days of booster vaccination was profoundly increased, relative to the response at corresponding times after priming. Thus, there was a striking increase in the: (i) frequency of CD14+CD16+ inflammatory monocytes; (ii) concentration of IFN- y in the plasma, which correlated with enhanced pSTAT3 and pSTAT1 levels in monocytes and T cells; and (iii) transcriptional signatures of innate responses characteristic of antiviral vaccine responses against pandemic influenza, HIV and Ebola, within 2 days following booster vaccination compared to primary vaccination. Consistent with these observations, single-cell transcriptomics analysis of 242,479 leukocytes demonstrated a ~100-fold increase in the frequency of a myeloid cluster, enriched in a signature of interferon-response transcription factors (TFs) and reduced in AP-1 TFs, one day after secondary immunization, at day 21. Finally, we delineated distinct molecular pathways of innate activation that correlate with CD8 T cell and nAb responses and identified an early monocyte-related signature that was associated with the breadth of the nAb response against the B1.351 variant strain. Collectively, these data provide insights into the immune responses induced by mRNA vaccines and demonstrate their capacity to stimulate an enhanced innate response following booster immunization.

    View details for DOI 10.21203/rs.3.rs-438662/v1

    View details for PubMedID 34013244

    View details for PubMedCentralID PMC8132234

  • H2-antagonist in IgE-mediated type I hypersensitivity reactions: what literature says so far? Clinical and molecular allergy : CMA Borro, M., Negrini, S., Long, A., Chinthrajah, S., Murdaca, G. 2021; 19 (1): 4

    Abstract

    Histamine is a monoamine synthesized from the amino acid histidine that is well-known for its role in IgE-mediated anaphylaxis but has shown pleiotropic effects on the immune system, especially in order to promote inflammatory responses. H1-receptor antagonist are common drugs used in mild/moderate allergic reactions whereas H2-receptor antagonist are commonly administered in gastric ulcer but showed some properties in allergy too. The EAACI guidelines for diagnosis and treatment of anaphylactic reactions recommend their use as third-line therapy in adjunct to H1-antagonists. The purpose of this article is to produce a complete summary of findings and evidence known so far about the usefulness of H2-receptor antagonist in allergic reactons.

    View details for DOI 10.1186/s12948-021-00143-y

    View details for PubMedID 33849573

  • Vaccines and Allergic reactions: the past, the current COVID-19 pandemic, and future perspectives. Allergy Sampath, V., Rabinowitz, G., Shah, M., Jain, S., Diamant, Z., Jesenak, M., Rabin, R., Vieths, S., Agache, I., Akdis, M., Barber, D., Breiteneder, H., Chinthrajah, S., Chivato, T., Collins, W., Eiwegger, T., Fast, K., Fokkens, W., O'Hehir, R. E., Ollert, M., O'Mahony, L., Palomares, O., Pfaar, O., Riggioni, C., Shamji, M. H., Sokolowska, M., Torres, M. J., Traidl-Hoffmann, C., van Zelm, M., Wang, D. Y., Zhang, L., Akdis, C., Nadeau, K. C. 2021

    Abstract

    Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur aftervaccination and individual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post-authorization and post-marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for individual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research.

    View details for DOI 10.1111/all.14840

    View details for PubMedID 33811364

  • Immune Changes Beyond Th2 Pathways During Rapid Multifood Immunotherapy enabled with Omalizumab. Allergy Manohar, M., Dunham, D., Gupta, S., Yan, Z., Zhang, W., Minnicozzi, S., Kirkey, M., Bunning, B., Chowdhury, R. R., Galli, S. J., Boyd, S. D., Kost, L. E., Chinthrajah, R. S., Desai, M., Oettgen, H. C., Maecker, H. T., Yu, W., DeKruyff, R. H., Andorf, S., Nadeau, K. C. 2021

    Abstract

    BACKGROUND: Multifood Oral Immunotherapy (mOIT) with adjunctive anti-IgE (omalizumab, Xolair ) treatment affords safe, effective, and rapid desensitization to multiple foods, although the specific immune mechanisms mediating this desensitization remain to be fully elucidated.METHODS: Participants in our phase 2 mOIT trial (NCT02643862) received omalizumab from baseline to week 16 and mOIT from week 8 to week 36. We compared the immune profile of PBMCs and plasma taken at baseline, week 8 and week 36 using high-dimensional mass cytometry, component-resolved diagnostics, the indirect basophil activation test, and Luminex.RESULTS: We found (i) decreased frequency of IL4+ peanut-reactive CD4+ T cells and a marked downregulation of GPR15 expression and CXCR3 frequency among gammadelta and CD8+ T cell subsets at week 8 during the initial, omalizumab-alone induction phase; (ii) significant upregulation of the skin-homing receptor CCR4 in peanut-reactive CD4+ T and Th2 effector memory (EM) cells and of cutaneous lymphocyte-associated antigen (CLA) in peanut-reactive CD8+ T and CD8+ EM cells (iii) downregulation of CD86 expression among antigen-presenting cell subsets; and (iv) reduction in pro-inflammatory cytokines, notably IL-17, at week 36 post-OIT. We also observed significant attenuation of the Th2 phenotype post-OIT, defined by downregulation of IL-4 peanut-reactive T cells and OX40 in Th2EM cells, increased allergen component-specific IgG4/IgE ratio, and decreased allergen-driven activation of indirectly sensitized basophils.CONCLUSIONS: This exploratory study provides novel comprehensive insight into the immune underpinnings of desensitization through omalizumab-facilitated mOIT. Moreover, this study provides encouraging results to support the complex immune changes that can be induced by OIT.

    View details for DOI 10.1111/all.14833

    View details for PubMedID 33782956

  • SARS-CoV-2 infection and COVID-19 in asthmatics: a complex relationship. Nature reviews. Immunology Skevaki, C., Karsonova, A., Karaulov, A., Fomina, D., Xie, M., Chinthrajah, S., Nadeau, K. C., Renz, H. 2021

    View details for DOI 10.1038/s41577-021-00516-z

    View details for PubMedID 33623123

  • Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19. bioRxiv : the preprint server for biology Feyaerts, D., Hédou, J., Gillard, J., Chen, H., Tsai, E. S., Peterson, L. S., Ando, K., Manohar, M., Do, E., Dhondalay, G. K., Fitzpatrick, J., Artandi, M., Chang, I., Snow, T. T., Chinthrajah, R. S., Warren, C. M., Wittman, R., Meyerowitz, J. G., Ganio, E. A., Stelzer, I. A., Han, X., Verdonk, F., Gaudillière, D. K., Mukherjee, N., Tsai, A. S., Rumer, K. K., Jiang, S., Valdés Ferrer, S. I., Kelly, J. D., Furman, D., Aghaeepour, N., Angst, M. S., Boyd, S. D., Pinsky, B. A., Nolan, G. P., Nadeau, K. C., Gaudillière, B., McIlwain, D. R. 2021

    Abstract

    The biological determinants of the wide spectrum of COVID-19 clinical manifestations are not fully understood. Here, over 1400 plasma proteins and 2600 single-cell immune features comprising cell phenotype, basal signaling activity, and signaling responses to inflammatory ligands were assessed in peripheral blood from patients with mild, moderate, and severe COVID-19, at the time of diagnosis. Using an integrated computational approach to analyze the combined plasma and single-cell proteomic data, we identified and independently validated a multivariate model classifying COVID-19 severity (multi-class AUCtraining = 0.799, p-value = 4.2e-6; multi-class AUCvalidation = 0.773, p-value = 7.7e-6). Features of this high-dimensional model recapitulated recent COVID-19 related observations of immune perturbations, and revealed novel biological signatures of severity, including the mobilization of elements of the renin-angiotensin system and primary hemostasis, as well as dysregulation of JAK/STAT, MAPK/mTOR, and NF-κB immune signaling networks. These results provide a set of early determinants of COVID-19 severity that may point to therapeutic targets for the prevention of COVID-19 progression.

    View details for DOI 10.1101/2021.02.09.430269

    View details for PubMedID 33594362

    View details for PubMedCentralID PMC7885914

  • Virtual Reality Reduces Pediatric Anxiety During Food Allergy Clinical Trials: A Pilot Randomized, Pragmatic Study. Frontiers in allergy Alonzi, S., Caruso, T. J., Sindher, S. B., Cao, S., Varadharajulu, S., Collins, W. J., Chinthrajah, R. S. 2021; 2: 779804

    Abstract

    Phlebotomy procedures required in food allergy (FA) diagnosis and clinical trials often induce fear and anxiety for pediatric patients. The primary aim of this study was to determine whether virtual reality (VR) applications were effective in reducing anxiety for pediatric FA patients undergoing phlebotomy during FA clinical trials. Secondary aims assessed fear, pain, procedural compliance, and adverse events. Participants undergoing phlebotomy were enrolled and randomized to a VR group or standard of care (SOC) group for this prospective pilot randomized, pragmatic study. Participants in the VR group played interactive applications on a customized Samsung Gear VR headset and those in the SOC group received the standard of care. Participants' anxiety, fear, and pain were assessed with the Children's Anxiety Meter, Children's Fear Scale, and FACES pain scale pre, during, and post phlebotomy procedure. Compliance was assessed using the modified Induction Compliance Checklist during the procedure and compared between two groups. Forty-nine participants were randomized to VR (n = 26) and SOC (n = 23) groups. Although both the VR and SOC groups experienced a decrease in anxiety and fear from pre- to post-procedure, those in the VR group experienced less anxiety and fear during the procedure than SOC participants. Similarly, both groups experienced an increase in pain from pre- to post-procedure; however, the VR group reported less pain during the procedure than SOC. Fewer symptoms of procedural non-compliance were reported in the VR group. Interactive VR applications may be an effective tool for reducing fear, anxiety, and pain during phlebotomy for FA clinical trials.

    View details for DOI 10.3389/falgy.2021.779804

    View details for PubMedID 35387040

    View details for PubMedCentralID PMC8974765

  • Bayesian Hierarchical Evaluation of Dose-Response for Peanut Allergy in Clinical Trial Screening. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association Haber, L. T., Reichard, J. F., Henning, A. K., Dawson, P. n., Chinthrajah, R. S., Sindher, S. B., Long, A. n., Vincent, M. J., Nadeau, K. C., Allen, B. C. 2021: 112125

    Abstract

    Risk-based labeling based on the minimal eliciting doses (EDs) in sensitized populations is a potential replacement for precautionary allergen labeling of food allergens. We estimated the dose-response distribution for peanut allergen using data from double-blind placebo-controlled food challenges (DBPCFCs) conducted in the US at multiple sites, testing a population believed to be similar to the general U.S. food allergic population. Our final (placebo-adjusted) dataset included 548 challenges of 481 subjects. Bayesian hierarchical analysis facilitated model fitting, and accounted for variability associated with various levels of data organization. The data are best described using a complex hierarchical structure that accounts for inter-individual variability and variability across study locations or substudies. Bayesian model averaging could simultaneously consider the fit of multiple models, but the Weibull model dominated so strongly that model averaging was not needed. The ED01 and ED05 (and 95% credible intervals) are 0.052 (0.021, 0.13) and 0.49 (0.22, 0.97) mg peanut protein, respectively. Accounting for challenges with severe reactions at the LOAEL, by using the dose prior to the LOAEL as the new LOAEL, the ED01 drops to 0.029 (0.014, 0.074) mg peanut protein. Our results could aid in establishing improved food labeling guidelines in the management of food allergies.

    View details for DOI 10.1016/j.fct.2021.112125

    View details for PubMedID 33722597

  • Peanut can be used as a reference allergen for hazard characterization in food allergen risk management: A rapid evidence assessment and meta-analysis. The journal of allergy and clinical immunology. In practice Turner, P. J., Patel, N., Ballmer-Weber, B. K., Baumert, J. L., Blom, W. M., Brooke-Taylor, S., Brough, H., Campbell, D. E., Chen, H., Chinthrajah, R. S., Crevel, R. W., Dubois, A. E., Ebisawa, M., Elizur, A., Gerdts, J. D., Gowland, M. H., Houben, G. F., Hourihane, J. O., Knulst, A. C., La Vieille, S., López, M. C., Mills, E. N., Polenta, G. A., Purington, N., Said, M., Sampson, H. A., Schnadt, S., Södergren, E., Taylor, S. L., Remington, B. C. 2021

    Abstract

    Regional and national legislation mandates the disclosure of "priority" allergens when present as an ingredient in foods, but this does not extend to the unintended presence of allergens due to shared production facilities. This has resulted in a proliferation of precautionary allergen ("may contain") labels (PAL) which are frequently ignored by food-allergic consumers. Attempts have been made to improve allergen risk management to better inform the use of PAL, but a lack of consensus has led to variety of regulatory approaches and non-uniformity in the use of PAL by food businesses. One potential solution would be to establish internationally-agreed "reference doses", below which no PAL would be needed. However, if reference doses are to be used to inform the need for PAL, then it is essential to characterize the hazard associated with these low-level exposures. For peanut, there are now published data relating to over 3000 double-blind, placebo-controlled challenges in allergic individuals, but a similar level of evidence is lacking for other priority allergens. We present the results of a rapid evidence assessment and meta-analysis for the risk of anaphylaxis to low-level allergen exposure for priority allergens. On the basis of this analysis, we propose that peanut can and should be considered an exemplar allergen for the hazard characterization at low-level allergen exposure.

    View details for DOI 10.1016/j.jaip.2021.08.008

    View details for PubMedID 34438104

  • Systems vaccinology of the BNT162b2 mRNA vaccine in humans. Nature Arunachalam, P. S., Scott, M. K., Hagan, T., Li, C., Feng, Y., Wimmers, F., Grigoryan, L., Trisal, M., Edara, V. V., Lai, L., Chang, S. E., Feng, A., Dhingra, S., Shah, M., Lee, A. S., Chinthrajah, S., Sindher, S. B., Mallajosyula, V., Gao, F., Sigal, N., Kowli, S., Gupta, S., Pellegrini, K., Tharp, G., Maysel-Auslender, S., Hamilton, S., Aoued, H., Hrusovsky, K., Roskey, M., Bosinger, S. E., Maecker, H. T., Boyd, S. D., Davis, M. M., Utz, P. J., Suthar, M. S., Khatri, P., Nadeau, K. C., Pulendran, B. 2021

    Abstract

    The emergency use authorization of two mRNA vaccines in less than a year since the emergence of SARS-CoV-2 represents a landmark in vaccinology1,2. Yet, how mRNA vaccines stimulate the immune system to elicit protective immune responses is unknown. Here we used a systems vaccinology approach to comprehensively profile the innate and adaptive immune responses of 56 healthy volunteers vaccinated with the Pfizer-BioNTech mRNA vaccine. Vaccination resulted in robust production of neutralizing antibodies (nAbs) against the parent Wuhan strain and, to a lesser extent, the B.1.351 strain, and significant increases in antigen-specific polyfunctional CD4 and CD8 T cells after the second dose. Booster vaccination stimulated a strikingly enhanced innate immune response compared to primary vaccination, evidenced by a greater: (i) frequency of CD14+CD16+ inflammatory monocytes; (ii) concentration of plasma IFN-g; (iii) transcriptional signature of innate antiviral immunity. Consistent with these observations, single-cell transcriptomics analysis demonstrated a ~100-fold increase in the frequency of a myeloid cell cluster, enriched in interferon-response transcription factors (TFs) and reduced in AP-1 TFs, following secondary immunization. Finally, we identified distinct innate pathways associated with CD8 T cell and nAb responses, and show that a monocyte-related signature correlates with the nAb response against the B.1.351 variant strain. Collectively, these data provide insights into immune responses induced by mRNA vaccination and demonstrate its capacity to prime the innate immune system to mount a more potent response following booster immunization.

    View details for DOI 10.1038/s41586-021-03791-x

    View details for PubMedID 34252919

  • Using data from food challenges to inform management of food-allergic consumers: a systematic review with individual participant data meta-analysis. The Journal of allergy and clinical immunology Patel, N. n., Adelman, D. C., Anagnostou, K. n., Baumert, J. L., Blom, W. M., Campbell, D. E., Chinthrajah, R. S., Mills, E. N., Javed, B. n., Purington, N. n., Remington, B. C., Sampson, H. A., Smith, A. D., Yarham, R. A., Turner, P. J. 2021

    Abstract

    Eliciting doses (e.g. ED01 or ED05 values, the amount of allergen expected to cause objective symptoms in 1% and 5% of the allergic population) are increasingly used to inform allergen labelling and clinical management. These values are generated from food challenge, but the frequency of anaphylaxis to these low levels of allergen exposure and their reproducibility is unknown.To determine (i) the rate of anaphylaxis to low level peanut exposure, and (ii) the reproducibility of reaction thresholds (and anaphylaxis) at food challenge.Systematic review and individual participant data (IPD) meta-analysis of studies reporting ≥50 peanut-allergic individuals reacting to peanut at double-blind, placebo-controlled food challenges (DBPCFC), published between January 2010 and September 2020. Risk of bias was assessed using National Institute for Clinical Excellence methodological checklists.Nineteen studies were included (total 3151 participants, 534 who subsequently underwent a further peanut challenge). At IPD meta-analysis, 4.5% (95%CI 1.9-10.1%) of individuals reacted to ≤5mg peanut protein with anaphylaxis (moderate heterogeneity [I2=57%]). Intra-individual thresholds varied by up to 3-log, although this was limited to a ½-log change in 71.2% (95%CI 56.2-82.6%). 2.4% (95%CI 1.1-5.0%) of patients initially tolerated 5mg peanut protein but then reacted to this dose at subsequent challenge (low heterogeneity, I2=16%); none had anaphylaxis.Around 5% of individuals reacting to an ED01 or ED05 level of exposure to peanut might have anaphylaxis to that dose. This equates to 1 and 6 anaphylaxis events per 2500 patients exposed to an ED01 or ED05 dose (respectively) in the broader peanut-allergic population.

    View details for DOI 10.1016/j.jaci.2021.01.025

    View details for PubMedID 33571537

  • COVID-19 pandemic: Practical considerations on the organization of an allergy clinic-An EAACI/ARIA Position Paper. Allergy Pfaar, O. n., Klimek, L. n., Jutel, M. n., Akdis, C. A., Bousquet, J. n., Breiteneder, H. n., Chinthrajah, S. n., Diamant, Z. n., Eiwegger, T. n., Fokkens, W. J., Fritsch, H. W., Nadeau, K. C., O'Hehir, R. E., O'Mahony, L. n., Rief, W. n., Sampath, V. n., Schedlowski, M. n., Torres, M. J., Traidl-Hoffmann, C. n., Wang, D. Y., Zhang, L. n., Bonini, M. n., Brehler, R. n., Brough, H. A., Chivato, T. n., Del Giacco, S. R., Dramburg, S. n., Gawlik, R. n., Gelincik, A. n., Hoffmann-Sommergruber, K. n., Hox, V. n., Knol, E. F., Lauerma, A. n., Matricardi, P. M., Mortz, C. G., Ollert, M. n., Palomares, O. n., Riggioni, C. n., Schwarze, J. n., Skypala, I. n., Untersmayr, E. n., Walusiak-Skorupa, J. n., Ansotegui, I. J., Bachert, C. n., Bedbrook, A. n., Bosnic-Anticevich, S. n., Brussino, L. n., Canonica, G. W., Cardona, V. n., Carreiro-Martins, P. n., Cruz, A. A., Czarlewski, W. n., Fonseca, J. A., Gotua, M. n., Haahtela, T. n., Ivancevich, J. C., Kuna, P. n., Kvedariene, V. n., Larenas-Linnemann, D. E., Abdul Latiff, A. H., Mäkelä, M. n., Morais-Almeida, M. n., Mullol, J. n., Naclerio, R. n., Ohta, K. n., Okamoto, Y. n., Onorato, G. L., Papadopoulos, N. G., Patella, V. n., Regateiro, F. S., Samoliński, B. n., Suppli Ulrik, C. n., Toppila-Salmi, S. n., Valiulis, A. n., Ventura, M. T., Yorgancioglu, A. n., Zuberbier, T. n., Agache, I. n. 2021; 76 (3): 648–76

    Abstract

    The coronavirus disease 2019 (COVID-19) has evolved into a pandemic infectious disease transmitted by the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Allergists and other healthcare providers (HCPs) in the field of allergies and associated airway diseases are on the front line, taking care of patients potentially infected with SARS-CoV-2. Hence, strategies and practices to minimize risks of infection for both HCPs and treated patients have to be developed and followed by allergy clinics.The scientific information on COVID-19 was analysed by a literature search in MEDLINE, PubMed, the National and International Guidelines from the European Academy of Allergy and Clinical Immunology (EAACI), the Cochrane Library, and the internet.Based on the diagnostic and treatment standards developed by EAACI, on international information regarding COVID-19, on guidelines of the World Health Organization (WHO) and other international organizations, and on previous experience, a panel of experts including clinicians, psychologists, IT experts, and basic scientists along with EAACI and the "Allergic Rhinitis and its Impact on Asthma (ARIA)" initiative have developed recommendations for the optimal management of allergy clinics during the current COVID-19 pandemic. These recommendations are grouped into nine sections on different relevant aspects for the care of patients with allergies.This international Position Paper provides recommendations on operational plans and procedures to maintain high standards in the daily clinical care of allergic patients while ensuring the necessary safety measures in the current COVID-19 pandemic.

    View details for DOI 10.1111/all.14453

    View details for PubMedID 32531110

    View details for PubMedCentralID PMC7323448

  • Basophil activation test shows high accuracy in the diagnosis of peanut and tree nut allergy: The Markers of Nut Allergy Study. Allergy Duan, L., Celik, A., Hoang, J. A., Schmidthaler, K., So, D., Yin, X., Ditlof, C. M., Ponce, M., Upton, J. E., Lee, J., Hung, L., Breiteneder, H., Palladino, C., Atkinson, A. R., Kim, V. H., Berenjy, A., Asper, M., Hummel, D., Wong, S., Alexanian-Farr, M., Magder, A., Chinthrajah, S. R., Mukai, K., Tsai, M., Nadeau, K., Galli, S. J., Ramani, A. K., Szepfalusi, Z., Eiwegger, T. 2020

    Abstract

    BACKGROUND: Peanut and tree nut allergies are the most important causes of anaphylaxis. Co-reactivity to more than one nut is frequent, and co-sensitization in the absence of clinical data is often obtained. Confirmatory oral food challenges (OFCs) are inconsistently performed.OBJECTIVE: To investigate the utility of the basophil activation test (BAT) in diagnosing peanut and tree nut allergy.METHODS: The Markers Of Nut Allergy Study (MONAS) prospectively enrolled patients aged 0.5-17 years with confirmed peanut and/or tree nut (almond, cashew, hazelnut, pistachio, walnut) allergy or sensitization fromCanadian (n=150) and Austrian (n=50) tertiary pediatric centers. BAT using %CD63+ basophils (SSClow/CCR3pos) as outcome was performed with whole blood samples stimulated with allergen extracts of each nut (0.001-1000ng/mL protein). BAT results were assessed against confirmed allergic status in a blinded fashion to develop a generalizable statistical model for comparisonto extract and marker allergen-specificIgE.RESULTS: A mixed effect model integrating BAT results for 10 and 100 ng/mL of peanut and individual tree nut extracts was optimal. The area under the ROC curve (AUROC) was 0.98 for peanut, 0.97 for cashew, 0.92 for hazelnut, 0.95 for pistachio, and 0.97 for walnut. The BAT outperformed sIgE testing for peanut or hazelnut and was comparable for walnut (AUROC 0.95, 0.94, 0.92) ina sub-analysis in sensitized patients undergoing OFC.CONCLUSIONS: BAT can predict allergic clinical status to peanut and tree nuts in multi-nut sensitized children and may reduce the need for high-risk OFCs in patients.

    View details for DOI 10.1111/all.14695

    View details for PubMedID 33300157

  • Identification of Pru du 6 as a potential marker allergen for almond allergy. Allergy Kabasser, S., Hafner, C., Chinthrajah, S., Sindher, S. B., Kumar, D., Kost, L. E., Long, A. J., Nadeau, K. C., Breiteneder, H., Bublin, M. 2020

    Abstract

    BACKGROUND: Oral food challenges have demonstrated that diagnosis of almond allergy based on extract-sIgE tests display low specificity. Molecular allergy diagnosis is expected to improve accuracy, but its value in diagnosing almond allergy remains unknown.OBJECTIVE: To identify relevant almond allergens and examine their ability to improve almond allergy diagnosis.METHODS: IgE-reactive proteins were purified from almond kernels. IgE-binding to almond extract and the allergens was analyzed by quantitative ELISA using sera from 18 subjects with a proven almond allergy. The control group consisted of sera from 18 subjects allergic to peanut and/or tree nuts but tolerant to almond.RESULTS: Three IgE-binding proteins were identified: legumin (Pru du 6), alpha-hairpinin (Pru du 8) and mandelonitrile lyase (Pru du 10). Positive IgE (≥0.35 kU/L) to almond extract showed 94% sensitivity but only 33% specificity. IgE to Pru du 6 maintained high sensitivity (83%) and provided superior specificity (78%). Sera from almond-allergic subjects had significantly higher IgE levels to almond extract (P<0.0001) and Pru du 6 (P<0.0001) than sera from tolerant donors. Sensitization to Pru du 6 was highly specific for almond allergy, while frequencies of sensitization to legumins from peanut, walnut, hazelnut, and cashew were similar in both groups. IgE to Pru du 8 and Pru du 10 was less sensitive (41% and 67%), but showed specificities of 100% and 61%.CONCLUSION: The use of almond allergens markedly increases the diagnostic specificity compared to the extract. Pru du 6 is a potential new molecular marker for almond allergy.

    View details for DOI 10.1111/all.14613

    View details for PubMedID 33020913

  • Long-term, open-label extension study of the efficacy and safety of epicutaneous immunotherapy for peanut allergy in children: PEOPLE 3-year results JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY Fleischer, D. M., Shreffler, W. G., Campbell, D. E., Green, T. D., Anvari, S., Assa'ad, A., Begin, P., Beyer, K., Bird, J., Brown-Whitehorn, T., Byrne, A., Chan, E. S., Cheema, A., Chinthrajah, S., Chong, H., Davis, C. M., Ford, L. S., Gagnon, R., Greenhawt, M., Hourihane, J., Jones, S. M., Kim, E. H., Lange, L., Lanser, B. J., Leonard, S., Mahler, V., Maronna, A., Nowak-Wegrzyn, A., Oriel, R. C., O'Sullivan, M., Petroni, D., Pongracic, J. A., Prescott, S. L., Schneider, L. C., Smith, P., Staab, D., Sussman, G., Wood, R., Yang, W. H., Lambert, R., Peillon, A., Bois, T., Sampson, H. A. 2020; 146 (4): 863–74
  • Intranasal corticosteroids in allergic rhinitis in COVID-19 infected patients: An ARIA-EAACI statement ALLERGY Bousquet, J., Akdis, C. A., Jutel, M., Bachert, C., Klimek, L., Agache, I., Ansotegui, I. J., Bedbrook, A., Bosnic-Anticevich, S., Canonica, G., Chivato, T., Cruz, A. A., Czarlewski, W., Del Giacco, S., Du, H., Fonseca, J. A., Gao, Y., Haahtela, T., Hoffmann-Sommergruber, K., Ivancevich, J., Khaltaev, N., Knol, E. F., Kuna, P., Larenas-Linnemann, D., Mullol, J., Naclerio, R., Ohta, K., Okamoto, Y., O'Mahony, L., Onorato, G. L., Papadopoulos, N. G., Pfaar, O., Samolinski, B., Schwarze, J., Toppila-Salmi, S., Ventura, M., Valiulis, A., Yorgancioglu, A., Zuberbier, T., Pawankar, R., ARIA MASK Study Grp 2020; 75 (10): 2440-2444

    View details for DOI 10.1111/all.14302

    View details for Web of Science ID 000583745600001

    View details for PubMedID 32233040

  • Editorial: Insights Into the Etiology, Prevention, and Treatment of Food Allergy. Frontiers in immunology Oyoshi, M., Chinthrajah, R. S. 2020; 11: 1937

    View details for DOI 10.3389/fimmu.2020.01937

    View details for PubMedID 32973797

    View details for PubMedCentralID PMC7473206

  • Transcriptional changes in peanut-specific CD4+ T cells over the course of oral immunotherapy. Clinical immunology (Orlando, Fla.) Wang, W., Lyu, S., Ji, X., Gupta, S., Manohar, M., Dhondalay, G. K., Chinthrajah, S., Andorf, S., Boyd, S. D., Tibshirani, R., Galli, S. J., Nadeau, K. C., Maecker, H. T. 2020: 108568

    Abstract

    Oral immunotherapy (OIT) can successfully desensitize allergic individuals to offending foods such as peanut. Our recent clinical trial (NCT02103270) of peanut OIT allowed us to monitor peanut-specific CD4+ T cells, using MHC-peptide Dextramers, over the course of OIT. We used a single-cell targeted RNAseq assay to analyze these cells at 0, 12, 24, 52, and 104 weeks of OIT. We found a transient increase in TGFbeta-producing cells at 52 weeks in those with successful desensitization, which lasted until 117 weeks. We also performed clustering and identified 5 major clusters of Dextramer+ cells, which we tracked over time. One of these clusters appeared to be anergic, while another was consistent with recently described TFH13 cells. The other 3 clusters appeared to be Th2 cells by their coordinated production of IL-4 and IL-13, but they varied in their expression of STAT signaling proteins and other markers. A cluster with high expression of STAT family members also showed a possible transient increase at week 24 in those with successful desensitization. Single cell TCRalphabeta repertoire sequences were too diverse to track clones over time. Together with increased TGFbeta production, these changes may be mechanistic predictors of successful OIT that should be further investigated.

    View details for DOI 10.1016/j.clim.2020.108568

    View details for PubMedID 32783912

  • Long-Term, Open-Label Extension Study of the Efficacy and Safety of Epicutaneous Immunotherapy for Peanut Allergy in Children: PEOPLE 3-Year Results. The Journal of allergy and clinical immunology Fleischer, D. M., Shreffler, W. G., Campbell, D. E., Green, T. D., Anvari, S., Assa'ad, A., Begin, P., Beyer, K., Bird, J. A., Brown-Whitehorn, T., Byrne, A., Chan, E. S., Cheema, A., Chinthrajah, S., Chong, H., Davis, C. M., Ford, L. S., Gagnon, R., Greenhawt, M., O'B Hourihane, J., Jones, S. M., Kim, E. H., Lange, L., Lanser, B. J., Leonard, S., Mahler, V., Maronna, A., Nowak-Wegrzyn, A., Oriel, R. C., O'Sullivan, M., Petroni, D., Pongracic, J. A., Prescott, S. L., Schneider, L. C., Smith, P., Staab, D., Sussman, G., Wood, R., Yang, W. H., Lambert, R., Peillon, A., Bois, T., Sampson, H. A. 2020

    Abstract

    BACKGROUND: We previously reported the safety and efficacy of epicutaneous immunotherapy (EPIT) for peanut allergy (250 mug, daily epicutaneous peanut protein; DBV712 250mug) in a 12-month randomized controlled study (PEPITES) of peanut-allergic children aged 4-11 years.OBJECTIVE: To assess interim safety and efficacy of an additional 2 years of EPIT from the ongoing (5-year treatment) open-label extension PEOPLE study.METHODS: Subjects who completed PEPITES were offered enrollment in PEOPLE. Following an additional 2 years of daily DBV712 250mug, subjects who had received DBV712 250mug in PEPITES underwent Month-36 double-blind, placebo-controlled, food challenge (DBPCFC) with an optional Month-38 sustained unresponsiveness (SU) assessment.RESULTS: 198 (93%) of 213 eligible subjects who had received DBV712 250mug in PEPITES entered PEOPLE, of whom 141 (71%) had assessable DBPCFC at Month 36. At Month 36, 51.8% (73/141) of subjects reached an eliciting dose (ED) of ≥1000 mg, compared with 40.4% (57/141) at Month 12. 75.9% (107/141) demonstrated increased ED compared to baseline. 13.5% (19/141) tolerated the full DBPCFC of 5444 mg. Median cumulative reactive dose increased from 144 to 944 mg. 18 subjects underwent an optional SU assessment; 14/18 (77.8%) maintained an ED of ≥1000 mg at Month 38. Local patch-site skin reactions were common but decreased over time. There was no treatment-related epinephrine use in years 2 or 3. Compliance was high (96.9%), and withdrawals due to treatment-related adverse events low (1%).CONCLUSION: These results demonstrate that daily EPIT treatment for peanut allergy beyond 1 year leads to continued response from a well-tolerated, simple-to-use regimen.

    View details for DOI 10.1016/j.jaci.2020.06.028

    View details for PubMedID 32659313

  • ARIA-EAACI statement on Asthma and COVID-19 (June 2, 2020). Allergy Bousquet, J., Jutel, M., Akdis, C. A., Klimek, L., Pfaar, O., Nadeau, K. C., Eiwegger, T., Bedbrook, A., Ansotegui, I. J., Anto, J. M., Bachert, C., Bateman, E. D., Bennoor, K. S., Berghea, E. C., Bergmann, K., Blain, H., Bonini, M., Bosnic-Anticevich, S., Boulet, L., Brussino, L., Buhl, R., Camargos, P., Canonica, G. W., Cardona, V., Casale, T., Chinthrajah, S., Akdis, M., Chivato, T., Christoff, G., Cruz, A. A., Czarlewski, W., Del Giacco, S., Du, H., El-Gamal, Y., Fokkens, W. J., Fonseca, J. A., Gao, Y., Gaga, M., Gemicioglu, B., Gotua, M., Haahtela, T., Halpin, D., Hamelmann, E., Hoffmann-Sommergruber, K., Humbert, M., Ilina, N., Ivancevich, J., Joos, G., Khaitov, M., Kirenga, B., Knol, E. F., Ko, F. W., Koskinen, S., Kowalski, M. L., Kraxner, H., Kudlay, D., Kuna, P., Kupczyk, M., Kvedariene, V., Abdul Latiff, A. H., Le, L. T., Levin, M., Larenas-Linnemann, D., Louis, R., Masjedi, M. R., Melen, E., Mihaltan, F., Milenkovic, B., Mohammad, Y., Morais-Almeida, M., Mullol, J., Namazova, L., Neffen, H., Nunes, E., O'Byrne, P., O'Hehir, R., O'Mahony, L., Ohta, K., Okamoto, Y., Onorato, G. L., Panzner, P., Papadopoulos, N. G., Passalacqua, G., Patella, V., Pawankar, R., Pham-Thi, N., Pigearias, B., Popov, T. A., Puggioni, F., Regateiro, F. S., Rolla, G., Rottem, M., Samolinski, B., Sastre, J., Schwarze, J., Sheikh, A., Scichilone, N., Soto-Quiros, M., Sova, M., Nicola, S., Stelmach, R., Suppli-Ulrik, C., Taborda-Barata, L., To, T., Tomazic, P., Toppila-Salmi, S., Tsiligianni, I., Usmani, O., Valiulis, A., Ventura, M. T., Viegi, G., Vontetsianos, T., Wang, D. Y., Williams, S., Wong, G. W., Yorgancioglu, A., Zernotti, M., Zidarn, M., Zuberbier, T., Agache, I. 2020

    View details for DOI 10.1111/all.14471

    View details for PubMedID 32588922

  • Identification of cross-reactive allergens in cashew- and pistachio-allergic children during oral immunotherapy. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology He, Z., Dongre, P., Lyu, S., Manohar, M., Chinthrajah, R. S., Galli, S. J., DeKruyff, R. H., Nadeau, K. C., Andorf, S. 2020

    Abstract

    It has been estimated that around 8% of the children in the U.S. suffer from food allergy and of those, 40% are allergic to multiple foods. Among tree nuts, allergies to pistachios are common in those with cashew nut allergy and multiple homologous allergenic components are shared between the two nuts. Three major allergens from cashew (Ana o 1 at 50 kDa, Ana o 2 major band at 33 kDa and minor band at 53 kDa, and Ana o 3 at 10 kDa) and five major allergens from pistachio (Pis v 1 at 7 kDa, Pis v 2 at 32 kDa, Pis v 3 at 50 kDa, Pis v 4 at 23 kDa, and Pis v 5 at 36 kDa) have been identified. Of those, Ana o 1 and Pis v 3, Ana o 2 and Pis v 2, Ana o 2 and Pis v 5, Ana o 3 and Pis v 1 have been recognized as homologues based on their sequence similarity and cross reactivity to IgE from the patients.

    View details for DOI 10.1111/pai.13258

    View details for PubMedID 32323379

  • RNA-Seq of Gastrointestinal Biopsies During Oral Immunotherapy Reveals Changes in IgA Pathway Zhang, W., Dhondalay, G., Hoh, R., Tupa, D., Bunning, B., Fernandez-Becker, N., Kambham, N., Boyd, S., Galli, S., Andorf, S., Manohar, M., Chinthrajah, S., Nadeau, K. MOSBY-ELSEVIER. 2020: AB132
  • A Phase 2 Study of Multi Oral Immunotherapy in Multi Food Allergic Patients to Test Immune Markers after Minimum Maintenance Dose using Xolair Sindher, S., Kumar, D., Purington, N., Tupa, D., Long, A., Cao, S., Woch, M., Tan, T., Lloret, M., Chinthrajah, S., Nadeau, K. MOSBY-ELSEVIER. 2020: AB135
  • Quality Of Life in Patients with Food Allergy: A Systematic Review and Meta-Analysis of interventions Food Allergy Diagnosis and Immunotherapy Studies Cao, S., Borro, M., Sindher, S., Tupa, D., Long, A., Chinthrajah, S., Nadeau, K., Alonzi, S. MOSBY-ELSEVIER. 2020: AB245
  • The benefits of playing interactive games on virtual reality headsets during procedures in food allergy clinical trials Alonzi, S., Parikh, K., Varadharajulu, S., Chandra, S., Cao, S., Texeira, Z., Sindher, S., Nadeau, K., Chinthrajah, S. MOSBY-ELSEVIER. 2020: AB147
  • Skin TEWL results show significant improvements with Trilipid emollient compared to controls in infants and young children Nadeau, K., Sindher, S., Berdyshev, E., Shojinaga, M., Alkotob, S., Alonzi, S., Varadharajulu, S., Chandra, S., Chinthrajah, S., Brough, H., Chan, S., Lack, G., Leung, D. MOSBY-ELSEVIER. 2020: AB240
  • Perceived Burden of Treatment and Quality of Life in Long-Term Follow Up after Oral Immunotherapy in Food Allergic Patients Collins, W., Raeber, O., Tupa, D., Cao, S., Nadeau, K., Sindher, S., Chinthrajah, S. MOSBY-ELSEVIER. 2020: AB147
  • Protein Composition Changes in Manufactured Penaeus aztecus Shrimp Powder Chinthrajah, S., Johansson, J., Woch, M., Conn, T., Chen, E., Long, A., Lyu, S., Kumar, D., Sindher, S., Nadeau, K. MOSBY-ELSEVIER. 2020: AB226
  • Sustained outcomes in oral immunotherapy for peanut allergy (POISED study): a large, randomised, double-blind, placebo-controlled, phase 2 study Chinthrajah, S., Purington, N., Andorf, S., Long, A., O'Laughlin, K., Lyu, S., Manohar, M., Boyd, S., Tibshirani, R., Maecker, H., Mukai, K., Tsai, M., Desai, M., Galli, S., Nadeau, K. MOSBY-ELSEVIER. 2020: AB181
  • Dose-related Allergic Reactions Decrease Over Time During Peanut Oral Immunotherapy in a Large, Randomized, Double-blind, Placebo-controlled, Phase 2 Study Long, A., Purington, N., Andorf, S., O'Laughlin, K., Lyu, S., Sindher, S., Manohar, M., Boyd, S., Tibshirani, R., Maecker, H., Mukai, K., Tsai, M., Desai, M., Chinthrajah, S., Galli, S., Nadeau, K. MOSBY-ELSEVIER. 2020: AB134
  • Peanut oral immunotherapy induces gastrointestinal eosinophilia in a longitudinal randomized controlled trial Wright, B., Fernandez-Becker, N., Kambham, N., Purington, N., Cao, S., Tupa, D., Zhang, W., Rank, M., Kita, H., Katzka, D., Shim, K., Bunning, B., Doyle, A., Jacobsen, E., Boyd, S., Manohar, M., Galli, S., Nadeau, K., Chinthrajah, S. MOSBY-ELSEVIER. 2020: AB84
  • Th2A and Th17 cell frequencies and regulatory markers as follow-up biomarker candidates for successful multifood oral immunotherapy. Allergy Luce, S., Chinthrajah, S., Lyu, S. C., Nadeau, K., Mascarell, L. 2020

    View details for DOI 10.1111/all.14180

    View details for PubMedID 31930521

  • Legends of Allergy: Stephen J. Galli ALLERGY Tsai, M., Chinthrajah, S., Nadeau, K. C. 2020; 75 (1): 243–45

    View details for DOI 10.1111/all.13815

    View details for Web of Science ID 000506187800034

  • Increased diversity of gut microbiota during active oral immunotherapy in peanut allergic adults. Allergy He, Z. n., Vadali, V. G., Szabady, R. L., Zhang, W. n., Norman, J. M., Roberts, B. n., Tibshirani, R. n., Desai, M. n., Chinthrajah, R. S., Galli, S. J., Andorf, S. n., Nadeau, K. C. 2020

    View details for DOI 10.1111/all.14540

    View details for PubMedID 32750160

  • Gastrointestinal Eosinophil Responses in a Longitudinal, Randomized Trial of Peanut Oral Immunotherapy. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Wright, B. L., Fernandez-Becker, N. Q., Kambham, N. n., Purington, N. n., Cao, S. n., Tupa, D. n., Zhang, W. n., Sindher, S. B., Rank, M. A., Kita, H. n., Katzka, D. A., Shim, K. P., Bunning, B. J., Doyle, A. D., Jacobsen, E. A., Tsai, M. n., Boyd, S. D., Manohar, M. n., Chinthrajah, R. S. 2020

    Abstract

    Gastrointestinal side effects are common during oral immunotherapy (OIT) and eosinophilic esophagitis (EoE) is a potential complication. We aimed to characterize eosinophilic gastrointestinal responses to peanut OIT, in which peanut protein is given orally, with incremental increases in dose over time.Twenty adults with IgE-mediated peanut allergy were randomly assigned to groups given peanut OIT (n=15) or placebo (n=5); 1 additional subject withdrew before randomization. Serial gastrointestinal biopsies were collected at baseline (n=21, 0 weeks), following dose escalation (n=10, 52 weeks), and during the maintenance phase (n=11, 104 weeks). Endoscopic findings were characterized using the EoE endoscopic reference score. Biopsies were assessed for eosinophils per high-power field (eos/hpf) and other pathology features using EoE histologic scoring system scores. We performed immunohistochemical analyses of eosinophil peroxidase deposition, quantified using automated image analysis.At baseline, no subjects reported current gastrointestinal symptoms. However, 3 of the 21 subjects (14%) had esophageal peak eosinophil counts ≥15 eos/hpf and all subjects had dilated intercellular spaces (DIS). OIT induced or exacerbated esophageal eosinophilia (EE) at 52 weeks in most subjects (peak eosinophil counts >5 eos/hpf in 6 of 7 patients [86%]; peak eosinophil counts ≥15 eos/hpf in 4 of 7 patients [57%]). One subject met clinicopathologic criteria for EoE and withdrew; no significant changes in esophageal peak eosinophil counts were observed in the placebo group. EE in the OIT group corresponded with significant increases in EoE histologic scoring system scores and deposition of eosinophil peroxidase. In 4 of 6 participants (67%), OIT-induced EE and gastrointestinal eosinophilia resolved by the end of the maintenance phase. Gastrointestinal symptoms were not clearly associated with EE or gastrointestinal eosinophilia.In this pilot study, we found that peanut OIT-induced EE and gastrointestinal eosinophilia are usually transient and are not always associated with gastrointestinal symptoms. Clinicaltrials.gov no: NCT02103270.

    View details for DOI 10.1016/j.cgh.2020.05.019

    View details for PubMedID 32434067

  • Origins and clonal convergence of gastrointestinal IgE+ B cells in human peanut allergy. Science immunology Hoh, R. A., Joshi, S. A., Lee, J. Y., Martin, B. A., Varma, S. n., Kwok, S. n., Nielsen, S. C., Nejad, P. n., Haraguchi, E. n., Dixit, P. S., Shutthanandan, S. V., Roskin, K. M., Zhang, W. n., Tupa, D. n., Bunning, B. J., Manohar, M. n., Tibshirani, R. n., Fernandez-Becker, N. Q., Kambham, N. n., West, R. B., Hamilton, R. G., Tsai, M. n., Galli, S. J., Chinthrajah, R. S., Nadeau, K. C., Boyd, S. D. 2020; 5 (45)

    Abstract

    B cells in human food allergy have been studied predominantly in the blood. Little is known about IgE+ B cells or plasma cells in tissues exposed to dietary antigens. We characterized IgE+ clones in blood, stomach, duodenum, and esophagus of 19 peanut-allergic patients, using high-throughput DNA sequencing. IgE+ cells in allergic patients are enriched in stomach and duodenum, and have a plasma cell phenotype. Clonally related IgE+ and non-IgE-expressing cell frequencies in tissues suggest local isotype switching, including transitions between IgA and IgE isotypes. Highly similar antibody sequences specific for peanut allergen Ara h 2 are shared between patients, indicating that common immunoglobulin genetic rearrangements may contribute to pathogenesis. These data define the gastrointestinal tract as a reservoir of IgE+ B lineage cells in food allergy.

    View details for DOI 10.1126/sciimmunol.aay4209

    View details for PubMedID 32139586

  • Corrigendum: Analysis of a Large Standardized Food Challenge Data Set to Determine Predictors of Positive Outcome Across Multiple Allergens. Frontiers in immunology Sindher, S. n., Long, A. J., Purington, N. n., Chollet, M. n., Slatkin, S. n., Andorf, S. n., Tupa, D. n., Kumar, D. n., Woch, M. A., O'Laughlin, K. L., Assaad, A. n., Pongracic, J. n., Spergel, J. M., Tam, J. n., Tilles, S. n., Wang, J. n., Galli, S. J., Nadeau, K. C., Chinthrajah, R. S. 2020; 11: 625796

    Abstract

    [This corrects the article DOI: 10.3389/fimmu.2018.02689.].

    View details for DOI 10.3389/fimmu.2020.625796

    View details for PubMedID 33329616

    View details for PubMedCentralID PMC7734876

  • Consensus Report from the Food Allergy Research and Education (FARE) 2019 Oral Immunotherapy for Food Allergy Summit. The Journal of allergy and clinical immunology Pepper, A. N., Assa'ad, A. n., Blaiss, M. n., Brown, E. n., Chinthrajah, S. n., Ciaccio, C. n., Fasano, M. B., Gupta, R. n., Hong, N. n., Lang, D. n., Mahr, T. n., Malawer, E. n., Roach, A. n., Shreffler, W. n., Sicherer, S. n., Vickers, K. n., Vickery, B. P., Wasserman, R. n., Yates, K. n., Casale, T. B. 2020

    Abstract

    Food allergy is a major health problem affecting 5 to 10% of the population in developed nations, including an estimated 32 million Americans. Despite the large number of patients suffering from food allergies, up until the end of January 2020, no treatment for food allergies had been approved by the U.S. Food and Drug Administration (FDA). The only options were avoidance of food allergen triggers and acute management of allergic reactions. A considerable body of data exists supporting oral immunotherapy (OIT) as a promising, novel treatment option, including that for the now FDA-approved peanut OIT product, Palforzia. However, data for long-term quality of life improvement with OIT varies, depending on the measures used for analysis. Like many therapies, OIT is not without potential harms, and burdens, and the evaluation of patient-specific risk-benefit ratio of food OIT produces challenges for clinicians and patients alike, with many unanswered questions. Food Allergy Research & Education (FARE) organized the Oral Immunotherapy for Food Allergy Summit on November 6, 2019 modeled after the PRACTALL sessions between the European Academy of Allergy and Clinical Immunology (EAACI) and the American Academy of Allergy, Asthma and Immunology (AAAAI) to address these critical issues. Health care providers, patient representatives, researchers, regulators and food allergy advocates came together to discuss OIT and identify areas of common ground as well as gaps in existing research and areas of uncertainty and disagreement. The purpose of this paper is to summarize that discussion and facilitate collaboration among clinicians and patients to help them make better-informed decisions about offering and accepting OIT, respectively, as a therapeutic option.

    View details for DOI 10.1016/j.jaci.2020.05.027

    View details for PubMedID 32505612

  • An evaluation of factors influencing response to epicutaneous immunotherapy for peanut allergy in the PEPITES trial. Allergy and asthma proceedings Fleischer, D. M., Chinthrajah, S. n., Scurlock, A. M., Campbell, D. E., Green, T. D., Bee, K. J., Peillon, A. n., Ocheltree, T. n., Sampson, H. A. 2020; 41 (5): 326–35

    Abstract

    Background: Epicutaneous immunotherapy (EPIT) for peanut allergy is a potential novel immunotherapy that utilizes the unique cutaneous immunologic properties to induce desensitization. A randomized, double-blind, placebo-controlled Phase 3 trial (PEPITES) in peanut-allergic children 4-11 years demonstrated an epicutaneous patch (DBV712) with 250 µg peanut protein was statistically superior to placebo in inducing desensitization following 12 months of daily treatment. Objective: To investigate what baseline and in-study factors influenced response to DBV712 250 µg, with a focus on patch adhesion, by posthoc analysis of PEPITES data. Methods: A posthoc multivariate model built with log-transformed Month 12 eliciting dose (ED) as the dependent variable was used to assess the influence of baseline characteristics and patch adhesion. Baseline characteristics and treatment response were also evaluated by stratifying subjects into decile subgroups by patch detachment rates over the 12-month study. Results: Multivariate analysis identified higher baseline ED and lower baseline peanut-specific IgE as the variables most predictive of higher Month 12 ED, followed by mean daily patch application duration, baseline SCORing Atopic Dermatitis (SCORAD) score, and age. By decile stratification, no association between patch detachment and treatment response was identified for 80% of DBV712-treated subjects. All DBV712-treated subjects, including those with the highest patch detachment rates, demonstrated treatment benefit measured by fold-changes in geometric mean ED. Conclusion: We identified subject baseline characteristics of higher baseline ED and lower baseline peanut-specific IgE as most predictive of higher Month 12 ED. For the majority of treated subjects, patch detachment did not impact treatment response. A minority of subjects, highly sensitive to peanut at baseline, had lower prespecified responder rates and higher patch detachment rates, yet still benefited from treatment based upon fold-changes in ED.

    View details for DOI 10.2500/aap.2020.41.200047

    View details for PubMedID 32539908

  • Oral Immunotherapy and Basophil and Mast Cell Reactivity in Food Allergy. Frontiers in immunology Paranjape, A. n., Tsai, M. n., Mukai, K. n., Hoh, R. A., Joshi, S. A., Chinthrajah, R. S., Nadeau, K. C., Boyd, S. D., Galli, S. J. 2020; 11: 602660

    Abstract

    Basophil activation tests (BATs) can closely monitor, in vitro, a patient's propensity to develop type I hypersensitivity reactions. Because of their high specificity and sensitivity, BATs have become promising diagnostic tools, especially in cases with equivocal clinical histories, skin prick test results, and/or levels of specific IgE to allergen extracts. BATs also are useful as tools for monitoring the effects of treatment, since oral immunotherapy (OIT) studies report a diminution in patients' basophil responsiveness over the course of OIT. This review will discuss the BAT findings obtained before, during, and after OIT for food allergy. We will mainly focus on the association of basophil responsiveness, and alterations in basophil surface markers, with clinical outcomes and other clinical features, such as blood levels of specific IgG and IgE antibodies. The detailed analysis of these correlations will ultimately facilitate the use of BATs, along with other blood biomarkers, to differentiate short-term desensitization versus sustained unresponsiveness and to improve treatment protocols. Given the critical anatomic location of mast cells adjacent to the many IgE+ plasma cells found in the gastrointestinal tissues of allergic individuals, we will also discuss the role of gastrointestinal mast cells in manifestations of food allergies.

    View details for DOI 10.3389/fimmu.2020.602660

    View details for PubMedID 33381123

    View details for PubMedCentralID PMC7768812

  • Advancing Food Allergy Through Epidemiology: Understanding and Addressing Disparities in Food Allergy Management and Outcomes. The journal of allergy and clinical immunology. In practice Warren, C. M., Turner, P. J., Chinthrajah, R. S., Gupta, R. S. 2020

    Abstract

    Epidemiological studies have been pivotal in advancing understanding of the etiology of food allergy and in guiding the development of evidence-based guidelines for food allergy prevention and clinical management. In recent years, as research into the population-level distribution and determinants of food allergy has accumulated, data indicate that substantial differences in food allergy outcomes and management exist across racial/ethnic and other socioeconomic strata. This clinical commentary aims to provide a review of existing epidemiological studies and shed valuable light on the disparate burden of food allergy. Emerging methods to quantify environmental exposure and food allergy outcomes are detailed, as are specific areas in which future research is warranted. We also highlight the role that epidemiology plays in advancing health equity and provide a framework as to how it can effectively inform health policy at all phases of the policy cycle-from initial population health assessment to the evaluation and refinement of specific health policies (ie, national guidelines to promote earlier introduction of peanut-containing foods for allergy prevention).

    View details for DOI 10.1016/j.jaip.2020.09.064

    View details for PubMedID 33065370

  • Omalizumab in "non-IgE mediated" diseases. The Journal of allergy and clinical immunology Chinthrajah, R. S., Galli, S. J. 2020

    View details for DOI 10.1016/j.jaci.2020.10.033

    View details for PubMedID 33160970

  • A highly sensitive bioluminescent method for measuring allergen-specific IgE in microliter samples. Allergy Goyard, S. n., Balbino, B. n., Chinthrajah, R. S., Lyu, S. C., Janin, Y. L., Bruhns, P. n., Poncet, P. n., Galli, S. J., Nadeau, K. C., Reber, L. L., Rose, T. n. 2020

    View details for DOI 10.1111/all.14365

    View details for PubMedID 32407549

  • New Developments in Non-allergen-specific Therapy for the Treatment of Food Allergy. Current allergy and asthma reports Long, A. n., Borro, M. n., Sampath, V. n., Chinthrajah, R. S. 2020; 20 (1): 3

    Abstract

    The prevalence of food allergy is increasing. At the current time, there are no approved treatments for food allergy. Major limitations of immunotherapy are long treatment periods (months or years), frequent clinic visits, high costs, increased risk of adverse events during treatment, and lack of durability of desensitization. Additionally, it is allergen-specific, and in those allergic to multiple allergens, the length and cost of treatment are further increased. In this review, we summarize recent developments in novel non-allergen-specific treatments for food allergy.A number of monoclonal antibodies that block IgE or specific pro-allergenic cytokines or their receptors have shown promise in clinical trials for food allergy. The insight we have gained through the use of one drug for the treatment of an atopic disease is quickly being translated to other atopic diseases, including food allergy. The future for food allergy treatment with biologics looks bright.

    View details for DOI 10.1007/s11882-020-0897-8

    View details for PubMedID 31950290

  • Oral immunotherapy for peanut allergy: The pro argument. The World Allergy Organization journal Chinthrajah, R. S., Cao, S. n., Dunham, T. n., Sampath, V. n., Chandra, S. n., Chen, M. n., Sindher, S. n., Nadeau, K. n. 2020; 13 (8): 100455

    Abstract

    Food allergy (FA) is a growing public health problem with personal, social, nutritional, and economic consequences. In the United States, it is estimated that 8% of children and 10.8% of adults have food allergies. Allergies to peanuts are particularly worrisome as unlike allergies to other allergenic foods, such as milk and egg, which are commonly outgrown by 5 or 10 years of age, 80% of peanut allergies persist into adulthood. The first drug for peanut allergy, Palforzia, was approved by the US Food and Drug Administration (FDA) in January 2020. For other food allergies, the current standard of care for the management of FA is suboptimal and is limited to dietary elimination of the offending allergen, vigilance against accidental ingestion, and treatment of allergic reactions with antihistamines and epinephrine. However, dietary avoidance can be challenging, and it is estimated that approximately 40% of patients with food allergies report at least one food allergy-related emergency department in their lifetime. Reactions, even from minimal exposures, can be life-threatening. Oral immunotherapy (OIT) has been the best researched therapeutic approach for treating FA over the last decade, with clinical trials investigating its efficacy, safety, and ability to improve participants' quality of life (QoL). A number of studies and meta-analyses have shown that OIT treatment is effective in raising the threshold of reactivity to peanuts and other foods in addition to producing a measurable serum immune response to such therapy. Although OIT-related adverse events (AEs) are common during treatment, serious reactions are rare. In fact, while the majority of patients experience AEs related to dosing, most continue daily dosing in hopes of achieving protection against the culprit food. Moreover, the majority of participants report improvement of QoL after OIT and are positive about undergoing OIT. These results show patients' commitment to OIT and their optimism regarding the benefits of treatment. As a first step in therapeutic options to protect from reactions to unintentional ingestion of allergenic foods, and importantly, to address the many psychosocial aspects of living with FA, OIT shows promise. Future research will focus on identifying optimal OIT regimens that maintain protection after therapy and allow for regular food consumption without allergic symptoms. Education and informed shared decision making between patients and providers are essential in optimizing current therapy regimens.

    View details for DOI 10.1016/j.waojou.2020.100455

    View details for PubMedID 33005286

    View details for PubMedCentralID PMC7519204

  • Trends in egg specific immunoglobulin levels during natural tolerance and oral immunotherapy. Allergy Andorf, S., Bunning, B., Tupa, D., Cao, S., Long, A. J., Borres, M. P., Galli, S. J., Chinthrajah, R. S., Nadeau, K. C. 2019

    View details for DOI 10.1111/all.14107

    View details for PubMedID 31724180

  • Phase 2a randomized, placebo-controlled study of anti-IL-33 in peanut allergy. JCI insight Chinthrajah, S., Cao, S., Liu, C., Lyu, S., Sindher, S. B., Long, A., Sampath, V., Petroni, D., Londei, M., Nadeau, K. C. 2019; 4 (22)

    Abstract

    BACKGROUNDIL-33, found in high levels in participants with allergic disorders, is thought to mediate allergic reactions. Etokimab, an anti-IL-33 biologic, has previously demonstrated a good safety profile and favorable pharmacodynamic properties in many clinical studies.METHODSIn this 6-week placebo-controlled phase 2a study, we evaluated the safety and the ability of a single dose of etokimab to desensitize peanut-allergic adults. Participants received either etokimab (n = 15) or blinded placebo (n = 5). Clinical tests included oral food challenges and skin prick tests at days 15 and 45. Blood samples were collected for IgE levels and measurement of ex vivo peanut-stimulated T cell cytokine production.RESULTSEfficacy measurements for active vs. placebo participants at the day 15 and 45 food challenge (tolerating a cumulative 275 mg of peanut protein, which was the food challenge outcome defined in this paper) demonstrated, respectively, 73% vs. 0% (P = 0.008) to 57% vs. 0% (ns). The etokimab group had fewer adverse events compared with placebo. IL-4, IL-5, IL-9, IL-13, and ST2 levels in CD4+ T cells were reduced in the active vs. placebo arm upon peanut-induced T cell activation (P = 0.036 for IL-13 and IL-9 at day 15), and peanut-specific IgE was reduced in active vs. placebo (P = 0.014 at day 15).CONCLUSIONThe phase 2a results suggest etokimab is safe and well tolerated and that a single dose of etokimab could have the potential to desensitize peanut-allergic participants and possibly reduce atopy-related adverse events.TRIAL REGISTRATIONClinicalTrials.gov NCT02920021.FUNDINGThis work was supported by NIH grant R01AI140134, AnaptysBio, the Hartman Vaccine Fund, and the Sean N. Parker Center for Allergy and Asthma Research at Stanford University.

    View details for DOI 10.1172/jci.insight.131347

    View details for PubMedID 31723064

  • Conflicting verdicts on peanut OIT from the ICER and FDA Advisory Committee; where do we go from here? The Journal of allergy and clinical immunology Eiwegger, T., Anagnostou, K., Arasi, S., Begin, P., Ben-Shoshan, M., Beyer, K., Blumchen, K., Brough, H., Caubet, J., Chan, E. S., Chen, M., Chinthrajah, S., Davis, C. M., Roches, A. D., Du Toit, G., Elizur, A., Galli, S. J., Haland, G., Hoffmann-Sommergruber, K., Kim, H., Leung, D. Y., Long, A., Muraro, A., Nurmatov, U. B., Pajno, G. B., Sampath, V., Saxena, J., Sindher, S., Upton, J., Worm, M., Nadeau, K. 2019

    View details for DOI 10.1016/j.jaci.2019.10.021

    View details for PubMedID 31678426

  • Legends of Allergy: Stephen J. Galli. Allergy Tsai, M., Chinthrajah, S., Nadeau, K. C. 2019

    Abstract

    Professor Stephen J. Galli's rigorous and innovative research in the field of allergy and immunology has truly made him a legend in the field. His accomplishments are many as are the awards and recognitions he has received. He and his team have published approximately 430 peer-reviewed publications and 14 patents. He has chaired, organized, or co-organized 16 scientific meetings or symposia. Some of the major awards he has received are the MERIT award from NIAID/NIH (1995), Scientific Achievement Award from the International Association of Allergy and Clinical Immunology (1997), Scientific Achievement Award from the World Allergy Organization (2011), Rous-Whipple Award of the American Society for Investigative Pathology (2014), and the Karl Landsteiner Medal of the Austrian Society of Allergology and Immunology (2014). This article is protected by copyright. All rights reserved.

    View details for PubMedID 30964544

  • Effect of Epicutaneous Immunotherapy vs Placebo on Reaction to Peanut Protein Ingestion Among Children With Peanut Allergy: The PEPITES Randomized Clinical Trial. JAMA Fleischer, D. M., Greenhawt, M., Sussman, G., Begin, P., Nowak-Wegrzyn, A., Petroni, D., Beyer, K., Brown-Whitehorn, T., Hebert, J., Hourihane, J. O., Campbell, D. E., Leonard, S., Chinthrajah, R. S., Pongracic, J. A., Jones, S. M., Lange, L., Chong, H., Green, T. D., Wood, R., Cheema, A., Prescott, S. L., Smith, P., Yang, W., Chan, E. S., Byrne, A., Assa'ad, A., Bird, J. A., Kim, E. H., Schneider, L., Davis, C. M., Lanser, B. J., Lambert, R., Shreffler, W. 2019

    Abstract

    Importance: There are currently no approved treatments for peanut allergy.Objective: To assess the efficacy and adverse events of epicutaneous immunotherapy with a peanut patch among peanut-allergic children.Design, Setting, and Participants: Phase 3, randomized, double-blind, placebo-controlled trial conducted at 31 sites in 5 countries between January 8, 2016, and August 18, 2017. Participants included peanut-allergic children (aged 4-11 years [n=356] without a history of a severe anaphylactic reaction) developing objective symptoms during a double-blind, placebo-controlled food challenge at an eliciting dose of 300 mg or less of peanut protein.Interventions: Daily treatment with peanut patch containing either 250 mug of peanut protein (n=238) or placebo (n=118) for 12 months.Main Outcomes and Measures: The primary outcome was the percentage difference in responders between the peanut patch and placebo patch based on eliciting dose (highest dose at which objective signs/symptoms of an immediate hypersensitivity reaction developed) determined by food challenges at baseline and month 12. Participants with baseline eliciting dose of 10 mg or less were responders if the posttreatment eliciting dose was 300 mg or more; participants with baseline eliciting dose greater than 10 to 300 mg were responders if the posttreatment eliciting dose was 1000 mg or more. A threshold of 15% or more on the lower bound of a 95% CI around responder rate difference was prespecified to determine a positive trial result. Adverse event evaluation included collection of treatment-emergent adverse events (TEAEs).Results: Among 356 participants randomized (median age, 7 years; 61.2% male), 89.9% completed the trial; the mean treatment adherence was 98.5%. The responder rate was 35.3% with peanut-patch treatment vs 13.6% with placebo (difference, 21.7% [95% CI, 12.4%-29.8%; P<.001]). The prespecified lower bound of the CI threshold was not met. TEAEs, primarily patch application site reactions, occurred in 95.4% and 89% of active and placebo groups, respectively. The all-causes rate of discontinuation was 10.5% in the peanut-patch group vs 9.3% in the placebo group.Conclusions and Relevance: Among peanut-allergic children aged 4 to 11 years, the percentage difference in responders at 12 months with the 250-mug peanut-patch therapy vs placebo was 21.7% and was statistically significant, but did not meet the prespecified lower bound of the confidence interval criterion for a positive trial result. The clinical relevance of not meeting this lower bound of the confidence interval with respect to the treatment of peanut-allergic children with epicutaneous immunotherapy remains to be determined.Trial Registration: ClinicalTrials.gov Identifier: NCT02636699.

    View details for PubMedID 30794314

  • A Phase 2 Randomized Controlled Multisite Study Using Omalizumab-facilitated Rapid Desensitization to Test Continued vs Discontinued Dosing in Multifood Allergic Individuals. EClinicalMedicine Andorf, S. n., Purington, N. n., Kumar, D. n., Long, A. n., O'Laughlin, K. L., Sicherer, S. n., Sampson, H. n., Cianferoni, A. n., Whitehorn, T. B., Petroni, D. n., Makhija, M. n., Robison, R. G., Lierl, M. n., Logsdon, S. n., Desai, M. n., Galli, S. J., Rael, E. n., Assa'ad, A. n., Chinthrajah, S. n., Pongracic, J. n., Spergel, J. M., Tam, J. n., Tilles, S. n., Wang, J. n., Nadeau, K. n. 2019; 7: 27–38

    Abstract

    As there is limited data on the sustainability of desensitization of multifood-oral immunotherapy (multifood-OIT), we conducted a multisite multifood-OIT study to compare the efficacy of successful desensitization with sustained dosing vs discontinued dosing after multifood-OIT.We enrolled 70 participants, aged 5-22 years with multiple food allergies confirmed by double-blind placebo-controlled food challenges (DBPCFCs). In the open-label phase of the study, all participants received omalizumab (weeks 1-16) and multi-OIT (2-5 allergens; weeks 8-30) and eligible participants (on maintenance dose of each allergen by weeks 28-29) were randomized 1:1:1 to 1 g, 300 mg, or 0 mg arms (blinded, weeks 30-36) and then tested by food challenge at week 36. Success was defined as passing 2 g food challenge to at least 2 foods in week 36.Most participants were able to reach a dose of 2 g or higher of each of 2, 3, 4, and 5 food allergens (as applicable to the participant's food allergens in OIT) in week 36 food challenges. Using an intent-to-treat analysis, we did not find evidence that a 300 mg dose was effectively different than a 1 g dose in maintaining desensitization, and both together were more effective than OIT discontinuation (0 mg dose) (85% vs 55%, P = 0.03). Fifty-five percent of the intent-to-treat participants and 69% of per protocol participants randomized to the 0 mg arm showed no objective reactivity after 6 weeks of discontinuation. Cross-desensitization was found between cashew/pistachio and walnut/pecan when only one of the foods was part of OIT. No statistically significant safety differences were found between the three arms.These results suggest that sustained desensitization after omalizumab-facilitated multi-OIT best occurs through continued maintenance OIT dosing of either 300 mg or 1 g of each food allergen as opposed to discontinuation of multi-OIT.Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Jeff and MacKenzie Bezos, NIAID AADCRC U19AI104209.ClinicalTrials.gov number, NCT02626611.

    View details for DOI 10.1016/j.eclinm.2018.12.006

    View details for PubMedID 31193674

    View details for PubMedCentralID PMC6537534

  • ICER report for peanut OIT comes up short. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology Eiwegger, T. n., Anagnostou, K. n., Arasi, S. n., Bégin, P. n., Ben-Shoshan, M. n., Beyer, K. n., Blumchen, K. n., Brough, H. n., Caubet, J. C., Chan, E. S., Chinthrajah, S. n., Davis, C. M., Roches, A. D., Du Toit, G. n., Elizur, A. n., Galli, S. J., Håland, G. n., Hoffmann-Sommergruber, K. n., Kim, H. n., Leung, D. Y., Muraro, A. n., Nurmatov, U. B., Pajno, G. B., Sindher, S. n., Szepfalusi, Z. n., Torres, M. J., Upton, J. n., Worm, M. n., Nadeau, K. n. 2019

    View details for DOI 10.1016/j.anai.2019.09.001

    View details for PubMedID 31513908

  • Sustained Successful Peanut Oral Immunotherapy Associated with Low Basophil Activation and Peanut-Specific IgE. The Journal of allergy and clinical immunology Tsai, M. n., Mukai, K. n., Chinthrajah, R. S., Nadeau, K. C., Galli, S. J. 2019

    Abstract

    Oral immunotherapy (OIT) can successfully desensitize many peanut allergic subjects, but clinical tolerance diminishes over time upon discontinuation, or low dose maintenance, of peanut. Therefore, in order to improve the efficacy and sustainability of such therapy, we sought to identify biomarkers and clinical tools that can predict therapeutic outcomes and monitor treatment responses.We evaluated whether basophil activation in whole blood, and plasma levels of peanut-specific immunoglobulins, are useful biomarkers for peanut OIT.We longitudinally measured, before, during and after OIT, basophil activation in whole blood ex vivo in response to peanut stimulation, and peanut-specific IgE and IgG4, in a large, single-site, double-blind, randomized, placebo-controlled, phase 2 peanut OIT study. We compared basophil responsiveness and peanut specific immunoglobulins between those who were clinically reactive vs. tolerant to peanut oral challenges.Peanut OIT significantly decreased basophil activation, peanut-specific, Ara h 1, Ara h 2 and Ara h 3 IgEs, and sIgE/total IgE, but increased sIgG4/sIgE. Participants who became reactive to 4 g of peanut 13 weeks off active OIT exhibited higher peanut-induced basophil activation ex vivo and higher peanut-specific IgEs and sIgE/total IgE, but lower sIgG4/sIgE. Notably, participants entering the study with low basophil responsiveness were more likely to achieve treatment success. Substantial suppression of basophil activation was required to maintain long-term clinical tolerance after peanut OIT.Assessments of peanut-specific basophil activation and peanut-specific immunoglobulins can help to predict treatment outcomes, and to differentiate transient desensitization vs. sustained unresponsiveness after OIT.

    View details for DOI 10.1016/j.jaci.2019.10.038

    View details for PubMedID 31805311

  • Sustained outcomes in oral immunotherapy for peanut allergy (POISED study): a large, randomised, double-blind, placebo-controlled, phase 2 study. Lancet (London, England) Chinthrajah, R. S., Purington, N. n., Andorf, S. n., Long, A. n., O'Laughlin, K. L., Lyu, S. C., Manohar, M. n., Boyd, S. D., Tibshirani, R. n., Maecker, H. n., Plaut, M. n., Mukai, K. n., Tsai, M. n., Desai, M. n., Galli, S. J., Nadeau, K. C. 2019

    Abstract

    Dietary avoidance is recommended for peanut allergies. We evaluated the sustained effects of peanut allergy oral immunotherapy (OIT) in a randomised long-term study in adults and children.In this randomised, double-blind, placebo-controlled, phase 2 study, we enrolled participants at the Sean N Parker Center for Allergy and Asthma Research at Stanford University (Stanford, CA, USA) with peanut allergy aged 7-55 years with a positive result from a double-blind, placebo-controlled, food challenge (DBPCFC; ≤500 mg of peanut protein), a positive skin-prick test (SPT) result (≥5 mm wheal diameter above the negative control), and peanut-specific immunoglobulin (Ig)E concentration of more than 4 kU/L. Participants were randomly assigned (2·4:1·4:1) in a two-by-two block design via a computerised system to be built up and maintained on 4000 mg peanut protein through to week 104 then discontinued on peanut (peanut-0 group), to be built up and maintained on 4000 mg peanut protein through to week 104 then to ingest 300 mg peanut protein daily (peanut-300 group) for 52 weeks, or to receive oat flour (placebo group). DBPCFCs to 4000 mg peanut protein were done at baseline and weeks 104, 117, 130, 143, and 156. The pharmacist assigned treatment on the basis of a randomised computer list. Peanut or placebo (oat) flour was administered orally and participants and the study team were masked throughout by use of oat flour that was similar in look and feel to the peanut flour and nose clips, as tolerated, to mask taste. The statistician was also masked. The primary endpoint was the proportion of participants who passed DBPCFCs to a cumulative dose of 4000 mg at both 104 and 117 weeks. The primary efficacy analysis was done in the intention-to-treat population. Safety was assessed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02103270.Between April 15, 2014, and March 2, 2016, of 152 individuals assessed, we enrolled 120 participants, who were randomly assigned to the peanut-0 (n=60), peanut-300 (n=35), and placebo groups (n=25). 21 (35%) of peanut-0 group participants and one (4%) placebo group participant passed the 4000 mg challenge at both 104 and 117 weeks (odds ratio [OR] 12·7, 95% CI 1·8-554·8; p=0·0024). Over the entire study, the most common adverse events were mild gastrointestinal symptoms, which were seen in 90 of 120 patients (50/60 in the peanut-0 group, 29/35 in the peanut-300 group, and 11/25 in the placebo group) and skin disorders, which were seen in 50/120 patients (26/60 in the peanut-0 group, 15/35 in the peanut-300 group, and 9/25 in the placebo group). Adverse events decreased over time in all groups. Two participants in the peanut groups had serious adverse events during the 3-year study. In the peanut-0 group, in which eight (13%) of 60 participants passed DBPCFCs at week 156, higher baseline peanut-specific IgG4 to IgE ratio and lower Ara h 2 IgE and basophil activation responses were associated with sustained unresponsiveness. No treatment-related deaths occurred.Our study suggests that peanut OIT could desensitise individuals with peanut allergy to 4000 mg peanut protein but discontinuation, or even reduction to 300 mg daily, could increase the likelihood of regaining clinical reactivity to peanut. Since baseline blood tests correlated with week 117 treatment outcomes, this study might aid in optimal patient selection for this therapy.National Institute of Allergy and Infectious Diseases.

    View details for DOI 10.1016/S0140-6736(19)31793-3

    View details for PubMedID 31522849

  • Analysis of a Large Standardized Food Challenge Data Set to Determine Predictors of Positive Outcome Across Multiple Allergens. Frontiers in immunology Sindher, S., Long, A. J., Purington, N., Chollet, M., Slatkin, S., Andorf, S., Tupa, D., Kumar, D., Woch, M. A., O'Laughlin, K. L., Assaad, A., Pongracic, J., Spergel, J. M., Tam, J., Tilles, S., Wang, J., Galli, S. J., Nadeau, K. C., Chinthrajah, R. S. 2018; 9: 2689

    Abstract

    Background: Double-blind placebo-controlled food challenges (DBPCFCs) remain the gold standard for the diagnosis of food allergy; however, challenges require significant time and resources and place the patient at an increased risk for severe allergic adverse events. There have been continued efforts to identify alternative diagnostic methods to replace or minimize the need for oral food challenges (OFCs) in the diagnosis of food allergy. Methods: Data was extracted for all IRB-approved, Stanford-initiated clinical protocols involving standardized screening OFCs to a cumulative dose of 500 mg protein to any of 11 food allergens in participants with elevated skin prick test (SPT) and/or specific IgE (sIgE) values to the challenged food across 7 sites. Baseline population characteristics, biomarkers, and challenge outcomes were analyzed to develop diagnostic criteria predictive of positive OFCs across multiple allergens in our multi-allergic cohorts. Results: A total of 1247 OFCs completed by 427 participants were analyzed in this cohort. Eighty-five percent of all OFCs had positive challenges. A history of atopic dermatitis and multiple food allergies were significantly associated with a higher risk of positive OFCs. The majority of food-specific SPT, sIgE, and sIgE/total IgE (tIgE) thresholds calculated from cumulative tolerated dose (CTD)-dependent receiver operator curves (ROC) had high discrimination of OFC outcome (area under the curves > 0.75). Participants with values above the thresholds were more likely to have positive challenges. Conclusions: This is the first study, to our knowledge, to not only adjust for tolerated allergen dose in predicting OFC outcome, but to also use this method to establish biomarker thresholds. The presented findings suggest that readily obtainable biomarker values and patient demographics may be of use in the prediction of OFC outcome and food allergy. In the subset of patients with SPT or sIgE values above the thresholds, values appear highly predictive of a positive OFC and true food allergy. While these values are relatively high, they may serve as an appropriate substitute for food challenges in clinical and research settings.

    View details for DOI 10.3389/fimmu.2018.02689

    View details for PubMedID 30538699

    View details for PubMedCentralID PMC6277531

  • Baseline Gastrointestinal Eosinophilia Is Common in Oral Immunotherapy Subjects With IgE-Mediated Peanut Allergy. Frontiers in immunology Wright, B. L., Fernandez-Becker, N. Q., Kambham, N., Purington, N., Tupa, D., Zhang, W., Rank, M. A., Kita, H., Shim, K. P., Bunning, B. J., Doyle, A. D., Jacobsen, E. A., Boyd, S. D., Tsai, M., Maecker, H., Manohar, M., Galli, S. J., Nadeau, K. C., Chinthrajah, R. S. 2018; 9: 2624

    Abstract

    Rationale: Oral immunotherapy (OIT) is an emerging treatment for food allergy. While desensitization is achieved in most subjects, many experience gastrointestinal symptoms and few develop eosinophilic gastrointestinal disease. It is unclear whether these subjects have subclinical gastrointestinal eosinophilia (GE) at baseline. We aimed to evaluate the presence of GE in subjects with food allergy before peanut OIT. Methods: We performed baseline esophagogastroduodenoscopies on 21 adults before undergoing peanut OIT. Subjects completed a detailed gastrointestinal symptom questionnaire. Endoscopic findings were assessed using the Eosinophilic Esophagitis (EoE) Endoscopic Reference Score (EREFS) and biopsies were obtained from the esophagus, gastric antrum, and duodenum. Esophageal biopsies were evaluated using the EoE Histologic Scoring System. Immunohistochemical staining for eosinophil peroxidase (EPX) was also performed. Hematoxylin and eosin and EPX stains of each biopsy were assessed for eosinophil density and EPX/mm2 was quantified using automated image analysis. Results: All subjects were asymptomatic. Pre-existing esophageal eosinophilia (>5 eosinophils per high-power field [eos/hpf]) was present in five participants (24%), three (14%) of whom had >15 eos/hpf associated with mild endoscopic findings (edema, linear furrowing, or rings; median EREFS = 0, IQR 0-0.25). Some subjects also demonstrated basal cell hyperplasia, dilated intercellular spaces, and lamina propria fibrosis. Increased eosinophils were noted in the gastric antrum (>12 eos/hpf) or duodenum (>26 eos/hpf) in 9 subjects (43%). EPX/mm2 correlated strongly with eosinophil counts (r = 0.71, p < 0.0001). Conclusions: Pre-existing GE is common in adults with IgE-mediated peanut allergy. Eosinophilic inflammation (EI) in these subjects may be accompanied by mild endoscopic and histologic findings. Longitudinal data collection during OIT is ongoing.

    View details for DOI 10.3389/fimmu.2018.02624

    View details for PubMedID 30524424

    View details for PubMedCentralID PMC6261984

  • Eliciting Dose and Safety Outcomes From a Large Dataset of Standardized Multiple Food Challenges. Frontiers in immunology Purington, N., Chinthrajah, R. S., Long, A., Sindher, S., Andorf, S., O'Laughlin, K., Woch, M. A., Scheiber, A., Assa'ad, A., Pongracic, J., Spergel, J. M., Tam, J., Tilles, S., Wang, J., Galli, S. J., Desai, M., Nadeau, K. C. 2018; 9: 2057

    Abstract

    Background: Food allergy prevalence has continued to rise over the past decade. While studies have reported threshold doses for multiple foods, large-scale multi-food allergen studies are lacking. Our goal was to identify threshold dose distributions and predictors of severe reactions during blinded oral food challenges (OFCs) in multi-food allergic patients. Methods: A retrospective chart review was performed on all Stanford-initiated clinical protocols involving standardized screening OFCs to any of 11 food allergens at 7 sites. Interval-censoring survival analysis was used to calculate eliciting dose (ED) curves for each food. Changes in severity and ED were also analyzed among participants who had repeated challenges to the same food. Results: Of 428 participants, 410 (96%) had at least one positive challenge (1445 standardized OFCs with 1054 total positive challenges). Participants undergoing peanut challenges had the highest ED50 (29.9 mg), while those challenged with egg or pistachio had the lowest (7.07 or 1.7 mg, respectively). The most common adverse event was skin related (54%), followed by gastrointestinal (GI) events (33%). A history of asthma was associated with a significantly higher risk of a severe reaction (hazard ratio [HR]: 2.37, 95% confidence interval [CI]: 1.36, 4.13). Higher values of allergen-specific IgE (sIgE) and sIgE to total IgE ratio (sIgEr) were also associated with higher risk of a severe reaction (1.49 [1.19, 1.85] and 1.84 [1.30, 2.59], respectively). Participants undergoing cashew, peanut, pecan, sesame, and walnut challenges had more severe reactions as ED increased. In participants who underwent repeat challenges, the ED did not change (p = 0.66), but reactions were more severe (p = 0.02). Conclusions: Participants with a history of asthma, high sIgEr, and/or high values of sIgE were found to be at higher risk for severe reactions during food challenges. These findings may help to optimize food challenge dosing schemes in multi-food allergic, atopic patients, specifically at lower doses where the majority of reactions occur. Trials Registration Number: ClinicalTrials. gov number NCT03539692; https://clinicaltrials.gov/ct2/show/NCT03539692.

    View details for DOI 10.3389/fimmu.2018.02057

    View details for PubMedID 30298065

    View details for PubMedCentralID PMC6160556

  • Heterogeneity of Ara h Component-Specific CD4 T Cell Responses in Peanut-Allergic Subjects. Frontiers in immunology Renand, A., Farrington, M., Whalen, E., Wambre, E., Bajzik, V., Chinthrajah, S., Nadeau, K. C., Kwok, W. W. 2018; 9: 1408

    Abstract

    Understanding the peanut-specific CD4 T cell responses in peanut-allergic (PA) subjects should provide new insights into the development of innovative immunotherapies for the treatment of peanut allergy. Although peanut-specific CD4 T cells have a TH2 profile in PA subjects, the immunogenicity of different Ara h components in eliciting specific CD4 T cell responses and the heterogeneity of these Ara h-reactive TH2 cells remains unclear. In this study, we investigated Ara h 1, 2, 3, 6, and 8-specific T cell responses in PA and sensitized non-peanut-allergic (sNPA) subjects, using the CD154 upregulation assay and the class II tetramer technology. In the PA group, T cells directed against Ara h 1, 2, 3, and 6 have a heterogeneous TH2 phenotype characterized by differential expression of CRTH2, CD27, and CCR6. Reactivity toward these different components was also distinct for each PA subject. Two dominant Ara h 2 epitopes associated with DR1501 and DR0901 were also identified. Frequencies of Ara h-specific T cell responses were also linked to the peanut specific-IgE level. Conversely, low peanut-IgE level in sNPA subjects was associated with a weak or an absence of the allergen-specific T cell reactivity. Ara h 8-specific T cell reactivity was weak in both PA and sNPA subjects. Thus, peanut-IgE level was associated with a heterogeneous Ara h (but not Ara h 8)-specific T cell reactivity only in PA patients. This suggests an important immunogenicity of each Ara h 1, 2, 3, and 6 in inducing peanut allergy. Targeting Ara h 1-, 2-, 3-, and 6-specific effector-TH2 cells can be the future way to treat peanut allergy.

    View details for DOI 10.3389/fimmu.2018.01408

    View details for PubMedID 29988522

    View details for PubMedCentralID PMC6026622

  • Isotype-specific agglutination-PCR (ISAP): Asensitive and multiplex method for measuring allergen-specific IgE. The Journal of allergy and clinical immunology Tsai, C., Mukai, K., Robinson, P. V., Gray, M. A., Waschmann, M. B., Lyu, S., Tsai, M., Chinthrajah, R. S., Nadeau, K. C., Bertozzi, C. R., Galli, S. J. 2018; 141 (5): 1901

    View details for PubMedID 29248495

  • Isotype-specific agglutination-PCR (ISAP): A sensitive and multiplex method for measuring allergen-specific IgE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY Tsai, C., Mukai, K., Robinson, P. V., Gray, M. A., Waschmann, M. B., Lyu, S., Tsai, M., Chinthrajah, R. S., Nadeau, K. C., Bertozzi, C. R., Galli, S. J. 2018; 141 (5): 1901-+
  • Development of a tool predicting severity of allergic reaction during peanut challenge. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology Chinthrajah, R. S., Purington, N., Andorf, S., Rosa, J. S., Mukai, K., Hamilton, R., Smith, B. M., Gupta, R., Galli, S. J., Desai, M., Nadeau, K. C. 2018

    Abstract

    BACKGROUND: Reliable prognostic markers for predicting severity of allergic reactions during oral food challenges (OFC) have not been established.OBJECTIVE: We sought to develop a predictive algorithm of a food challenge severity score (CSS) to identify those at higher risk for severe reactions to a standardized peanut OFC.METHODS: Medical history and allergy tests were obtained for 120 peanut-allergic participants who underwent double-blind, placebo-controlled food challenges (DBPCFCs). Reactions were assigned a CSS between 1 to 6 based on cumulative tolerated dose and a "severity clinical indicator." Demographic characteristics, clinical features, peanut component IgE values, and a basophil activation marker were considered in a multi-step analysis to derive a flexible decision rule to understand risk during peanut of OFC.RESULTS: 18.3% participants had a severe reaction (CSS >4). The decision rule identified the following three variables (in order of importance) as predictors of reaction severity: ratio of %CD63hi stimulation with peanut to %CD63hi anti-IgE (CD63 ratio), history of exercise-induced asthma, and forced expiratory volume in 1 sec/forced vital capacity (FEV1/FVC) ratio. The CD63 ratio alone was a strong predictor of CSS (p<0.001).CONCLUSION: The CSS is a novel tool that combines dose thresholds and allergic reactions to understand risks associated with peanut OFCs. Lab-values (CD63 ratio), along with clinical variables (exercise-induced asthma and FEV1/FVC ratio) contribute to the predictive ability of the severity of reaction to peanut OFC. Further testing of this decision rule is needed in a larger external data source before it can be considered outside of research settings.

    View details for PubMedID 29709643

  • High dimensional immune biomarkers demonstrate differences in phenotypes and endotypes in food allergy and asthma. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology Chinthrajah, R. S., Purington, N., Sampath, V., Andorf, S., Manohar, M., Prunicki, M., Zhou, X., Tupa, D., Nadeau, K. C. 2018

    View details for PubMedID 29705381

  • Epigenetic Changes in Immune Cells Following Successful Desensitization with Multi-Food Allergen Oral Immunotherapy Chinthrajah, S., Andorf, S., Manohar, M., Maecker, H., Tsai, M., Galli, S., Nadeau, K. SPRINGER/PLENUM PUBLISHERS. 2018: 358–59
  • Anti-IgE treatment with oral immunotherapy in multifood allergic participants: a double-blind, randomised, controlled trial LANCET GASTROENTEROLOGY & HEPATOLOGY Andorf, S., Purington, N., Block, W. M., Long, A. J., Tupa, D., Brittain, E., Spergel, A., Desai, M., Galli, S. J., Nadeau, K. C., Chinthrajah, R. 2018; 3 (2): 85–94

    Abstract

    Despite progress in single food oral immunotherapy, there is little evidence concerning the safety and efficacy of treating individuals with multiple food (multifood) allergies. We did a pilot study testing whether anti-IgE (omalizumab) combined with multifood oral immunotherapy benefited multifood allergic patients.We did a blinded, phase 2 clinical trial at Stanford University. We enrolled participants, aged 4-15 years, with multifood allergies validated by double-blind, placebo-controlled food challenges to their offending foods. Inclusion criteria included a positive skin prick test of 6 mm or more (wheal diameter, above the negative control), a food-specific serum IgE concentration of more than 4 kU/L for each food, or both, and a positive double-blind, placebo-controlled food challenge at 500 mg or less of food protein. Exclusion criteria included eosinophilic oesophagitis and severe asthma. Participants were randomised (3:1) with a block size of four, to receive multifood oral immunotherapy to two to five foods, together with omalizumab (n=36) or placebo (n=12). 12 individuals who fulfilled the same inclusion and exclusion criteria were included as controls. These individuals were not randomised and received neither omalizumab nor oral immunotherapy. Omalizumab or placebo was administered subcutaneously for 16 weeks, with oral immunotherapy starting at week 8, and was stopped 20 weeks before the exit double-blind, placebo-controlled food challenge at week 36. The primary endpoint was the proportion of participants who passed double-blind, placebo-controlled food challenges to at least two of their offending foods. This completed trial is registered with ClinicalTrials.gov, number NCT02643862.Between March 25, 2015, and Aug 18, 2016, 165 participants were assessed for eligibility, of whom 84 did not meet the inclusion criteria and 21 declined to participate. We enrolled and randomised 48 eligible participants and the remaining 12 patients were included as nonrandomised, untreated controls. At week 36, a significantly greater proportion of the omalizumab-treated (30 [83%] of 36) versus placebo (four [33%] of 12) participants passed double-blind, placebo-controlled food challenges to 2 g protein for two or more of their offending foods (odds ratio 10·0, 95% CI 1·8-58·3, p=0·0044). All participants completed the study. There were no serious or severe (grade 3 or worse) adverse events. Participants in the omalizumab group had a significantly lower median per-participant percentage of oral immunotherapy doses associated with any adverse events (27% vs 68%; p=0·0082). The most common adverse events in both groups were gastrointestinal events.In multifood allergic patients, omalizumab improves the efficacy of multifood oral immunotherapy and enables safe and rapid desensitisation.US National Institutes of Health (NIH).

    View details for PubMedID 29242014

  • Changes in Binding Patterns of Cashew-Specific IgE and IgG4 Over the Course of Oral Immunotherapy with Omalizumab Stankey, C. T., Andorf, S., Tetteh, A., Chinthrajah, S., Nadeau, K. C. MOSBY-ELSEVIER. 2018: AB246
  • Peanut-specific type 1 regulatory T cells induced in vitro from allergic subjects are functionally impaired JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY Pellerin, L., Jenks, J., Chinthrajah, S., Dominguez, T., Block, W., Zhou, X., Noshirvan, A., Gregori, S., Roncarolo, M., Nadeau, K., Bacchetta, R. 2018; 141 (1): 202-+

    Abstract

    Peanut allergy (PA) is a life-threatening condition that lacks regulator-approved treatment. Regulatory T type 1 (TR1) cells are potent suppressors of immune responses and can be induced in vivo upon repeated antigen exposure or in vitro by using tolerogenic dendritic cells. Whether oral immunotherapy (OIT) leads to antigen-specific TR1 cell induction has not been established.We sought to determine whether peanut-specific TR1 cells can be generated in vitro from peripheral blood of patients with PA at baseline or during OIT and whether they are functional compared with peanut-specific TR1 cells induced from healthy control (HC) subjects.Tolerogenic dendritic cells were differentiated in the presence of IL-10 from PBMCs of patients with PA and HC subjects pulsed with the main peanut allergens of Arachis hypogaea, Ara h 1 and 2, and used as antigen-presenting cells for autologous CD4+ T cells (CD4+ T cells coincubated with tolerogenic dendritic cells pulsed with the main peanut allergens [pea-T10 cells]). Pea-T10 cells were characterized by the presence of CD49b+ lymphocyte-activation gene 3 (LAG3)+ TR1 cells, antigen-specific proliferative responses, and cytokine production.CD49b+LAG3+ TR1 cells were induced in pea-T10 cells at comparable percentages from HC subjects and patients with PA. Despite their antigen specificity, pea-T10 cells of patients with PA with or without OIT, as compared with those of HC subjects, were not anergic and had high TH2 cytokine production upon peanut-specific restimulation.Peanut-specific TR1 cells can be induced from HC subjects and patients with PA, but those from patients with PA are functionally defective independent of OIT. The unfavorable TR1/TH2 ratio is discussed as a possible cause of PA TR1 cell impairment.

    View details for PubMedID 28689791

  • Observational long-term follow-up study of rapid food oral immunotherapy with omalizumab ALLERGY ASTHMA AND CLINICAL IMMUNOLOGY Andorf, S., Manohar, M., Dominguez, T., Block, W., Tupa, D., Kshirsagar, R. A., Sampath, V., Chinthrajah, R., Nadeau, K. C. 2017; 13: 51

    Abstract

    A number of clinical studies focused on treating a single food allergy through oral immunotherapy (OIT) with adjunctive omalizumab treatment have been published. We previously demonstrated safety and tolerability of a rapid OIT protocol using omalizumab in a phase 1 study to achieve desensitization to multiple (up to 5) food allergens in parallel, rapidly (7-36 weeks; median = 18 weeks). In the current long-term, observational study, we followed 34 food allergic participants for over 5 years, who had originally undergone the phase 1 rapid OIT protocol.After reaching the maintenance dose of 2 g protein for each of their respective food allergens as a part of the phase 1 study, the long-term maintenance dose was reduced for some participants based on a pragmatic team-based decision. Participants were followed up to 62 months through standard oral food challenges (OFCs), skin prick tests, and blood tests.Each participant passed the 2 g OFC to each of their offending food allergens (up to 5 food allergens in total) at the end of the long-term follow-up (LTFU) study.Our data demonstrate the feasibility of long-term maintenance dosing of a food allergen without compromising the desensitized status conferred through rapid-OIT. Trial registration Registry: Clinicaltrials.gov. Registration numbers: NCT01510626 (original study), NCT03234764 (LTFU study). Date of registration: November 29, 2011 (original study); July 26, 2017 (LTFU study, retrospectively registered).

    View details for PubMedID 29296107

    View details for PubMedCentralID PMC5738812

  • Feasibility of sustained response through long-term dosing in food allergy immunotherapy ALLERGY ASTHMA AND CLINICAL IMMUNOLOGY Andorf, S., Manohar, M., Dominguez, T., Block, W., Tupa, D., Kshirsagar, R. A., Sampath, V., Chinthrajah, R., Nadeau, K. C. 2017; 13: 52

    Abstract

    Clinical trials using oral immunotherapy (OIT) for the treatment of food allergies have shown promising results. We previously demonstrated the feasibility of desensitization for up to 5 food allergens simultaneously through OIT. In this observational study, we report the findings of long-term follow-up (LTFU) of the participants treated through a single site OIT phase 1 trial.The participants (n = 46) were followed up to 72 months since the time they reached 2 g maintenance dose per food in the initial phase 1 trial. During the long-term maintenance dosing, participants continued or reduced the initial maintenance dose of food allergen protein to high (median 2 g protein) vs. low (median 300 mg protein). Participant follow-up included clinical monitoring, standardized OFCs, and in some cases, skin prick tests and measurement of allergen-specific IgE and IgG4.Irrespective of the high vs. low long-term maintenance dose during LTFU, all participants were able to ingest 2 g protein of each food allergen protein during OFCs performed at the end of our LTFU.Our LTFU cohort of food OIT participants from a single site, phase 1 OIT study, supports the feasibility of sustained desensitization through long-term maintenance dosing. Trial registration Registry: Clinicaltrial.gov. Registration numbers: NCT01490177 (original study); NCT03234764 (LTFU study). Date of registration: November 29, 2011 (original study); July 26, 2017 (LTFU study, registered).

    View details for PubMedID 29296108

    View details for PubMedCentralID PMC5738818

  • A new fluorescent-avidin-based method for quantifying basophil activation in whole blood JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY Mukai, K., Chinthrajah, R., Nadeau, K. C., Tsai, M., Gaudenzio, N., Galli, S. J. 2017; 140 (4): 1202-+

    View details for PubMedID 28606590

    View details for PubMedCentralID PMC5632583

  • Association of Clinical Reactivity with Sensitization to Allergen Components in Multifood-Allergic Children. journal of allergy and clinical immunology. In practice Andorf, S., Borres, M. P., Block, W., Tupa, D., Bollyky, J. B., Sampath, V., Elizur, A., Lidholm, J., Jones, J. E., Galli, S. J., Chinthrajah, R. S., Nadeau, K. C. 2017

    Abstract

    Thirty percent of children with food allergies have multiple simultaneous allergies; however, the features of these multiple allergies are not well characterized serologically or clinically.We comprehensively evaluated 60 multifood-allergic patients by measuring serum IgE to key allergen components, evaluating clinical histories and medication use, performing skin tests, and conducting double-blind, placebo-controlled food challenges (DBPCFCs).Sixty participants with multiple food allergies were characterized by clinical history, DBPCFCs, total IgE, specific IgE, and component-resolved diagnostics (IgE and IgG4) data. The food allergens tested were almond, egg, milk, sesame, peanut, pecan, walnut, hazelnut, cashew, pistachio, soy, and wheat.Our data demonstrate that of the reactions observed during a graded DBPCFC, gastrointestinal reactions occurred more often in boys than in girls, as well as in individuals with high levels of IgE to 2S albumins from cashew, walnut, and hazelnut. Certain food allergies often occurred concomitantly in individuals (ie, cashew/pistachio and walnut/pecan/hazelnut). IgE testing to components further corroborated serological relationships between and among these clustered food allergies.Associations of certain food allergies were shown by DBPCFC outcomes as well as by correlations in IgE reactivity to structurally related food allergen components. Each of these criteria independently demonstrated a significant association between allergies to cashew and pistachio, as well as among allergies to walnut, pecan, and hazelnut.

    View details for DOI 10.1016/j.jaip.2017.01.016

    View details for PubMedID 28351786

  • Assessing basophil activation by using flow cytometry and mass cytometry in blood stored 24 hours before analysis JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY Mukai, K., Gaudenzio, N., Gupta, S., Vivanco, N., Bendall, S. C., Maecker, H. T., Chinthrajah, R. S., Tsai, M., Nadeau, K. C., Galli, S. J. 2017; 139 (3): 889-?

    Abstract

    Basophil activation tests (BATs) have promise for research and for clinical monitoring of patients with allergies. However, BAT protocols vary in blood anticoagulant used and temperature and time of storage before testing, complicating comparisons of results from various studies.We attempted to establish a BAT protocol that would permit analysis of blood within 24 hours of obtaining the sample.Blood from 46 healthy donors and 120 patients with peanut allergy was collected into EDTA or heparin tubes, and samples were stored at 4°C or room temperature for 4 or 24 hours before performing BATs.Stimulation with anti-IgE or IL-3 resulted in strong upregulation of basophil CD203c in samples collected in EDTA or heparin, stored at 4°C, and analyzed 24 hours after sample collection. However, a CD63(hi) population of basophils was not observed in any conditions in EDTA-treated samples unless exogenous calcium/magnesium was added at the time of anti-IgE stimulation. By contrast, blood samples collected in heparin tubes were adequate for quantification of upregulation of basophil CD203c and identification of a population of CD63(hi) basophils, irrespective of whether the specimens were analyzed by means of conventional flow cytometry or cytometry by time-of-flight mass spectrometry, and such tests could be performed after blood was stored for 24 hours at 4°C.BATs to measure upregulation of basophil CD203c and induction of a CD63(hi) basophil population can be conducted with blood obtained in heparin tubes and stored at 4°C for 24 hours.

    View details for DOI 10.1016/j.jaci.2016.04.060

    View details for Web of Science ID 000397295800022

    View details for PubMedCentralID PMC5237629

  • Omalizumab facilitates rapid oral desensitization for peanut allergy JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY MacGinnitie, A. J., Rachid, R., Gragg, H., Little, S. V., Lakin, P., Cianferoni, A., Heimall, J., Makhija, M., Robison, R., Chinthrajah, R. S., Lee, J., LeBovidge, J., Dominguez, T., Rooney, C., Lewis, M. O., Koss, J., Burke-Roberts, E., Chin, K., Logvinenko, T., Pongracic, J. A., Umetsu, D. T., Spergel, J., Nadeau, K. C., Schneider, L. C. 2017; 139 (3): 873-?
  • Assessing basophil activation by using flow cytometry and mass cytometry in blood stored 24 hours before analysis. journal of allergy and clinical immunology Mukai, K., Gaudenzio, N., Gupta, S., Vivanco, N., Bendall, S. C., Maecker, H. T., Chinthrajah, R. S., Tsai, M., Nadeau, K. C., Galli, S. J. 2016

    Abstract

    Basophil activation tests (BATs) have promise for research and for clinical monitoring of patients with allergies. However, BAT protocols vary in blood anticoagulant used and temperature and time of storage before testing, complicating comparisons of results from various studies.We attempted to establish a BAT protocol that would permit analysis of blood within 24 hours of obtaining the sample.Blood from 46 healthy donors and 120 patients with peanut allergy was collected into EDTA or heparin tubes, and samples were stored at 4°C or room temperature for 4 or 24 hours before performing BATs.Stimulation with anti-IgE or IL-3 resulted in strong upregulation of basophil CD203c in samples collected in EDTA or heparin, stored at 4°C, and analyzed 24 hours after sample collection. However, a CD63(hi) population of basophils was not observed in any conditions in EDTA-treated samples unless exogenous calcium/magnesium was added at the time of anti-IgE stimulation. By contrast, blood samples collected in heparin tubes were adequate for quantification of upregulation of basophil CD203c and identification of a population of CD63(hi) basophils, irrespective of whether the specimens were analyzed by means of conventional flow cytometry or cytometry by time-of-flight mass spectrometry, and such tests could be performed after blood was stored for 24 hours at 4°C.BATs to measure upregulation of basophil CD203c and induction of a CD63(hi) basophil population can be conducted with blood obtained in heparin tubes and stored at 4°C for 24 hours.

    View details for DOI 10.1016/j.jaci.2016.04.060

    View details for PubMedID 27527263

    View details for PubMedCentralID PMC5237629

  • Molecular and cellular mechanisms of food allergy and food tolerance. journal of allergy and clinical immunology Chinthrajah, R. S., Hernandez, J. D., Boyd, S. D., Galli, S. J., Nadeau, K. C. 2016; 137 (4): 984-997

    Abstract

    Ingestion of innocuous antigens, including food proteins, normally results in local and systemic immune nonresponsiveness in a process termed oral tolerance. Oral tolerance to food proteins is likely to be intimately linked to mechanisms that are responsible for gastrointestinal tolerance to large numbers of commensal microbes. Here we review our current understanding of the immune mechanisms responsible for oral tolerance and how perturbations in these mechanisms might promote the loss of oral tolerance and development of food allergies. Roles for the commensal microbiome in promoting oral tolerance and the association of intestinal dysbiosis with food allergy are discussed. Growing evidence supports cutaneous sensitization to food antigens as one possible mechanism leading to the failure to develop or loss of oral tolerance. A goal of immunotherapy for food allergies is to induce sustained desensitization or even true long-term oral tolerance to food allergens through mechanisms that might in part overlap with those associated with the development of natural oral tolerance.

    View details for DOI 10.1016/j.jaci.2016.02.004

    View details for PubMedID 27059726

  • T-Cell Immunophenotyping of Second-Hand Smoke-related Asthma. Annals of the American Thoracic Society Bauer, R. N., Chinthrajah, R. S., Andorf, S., Hobson, B., Miller, R. L., Nadeau, K. C. 2016; 13: S95-?

    View details for DOI 10.1513/AnnalsATS.201507-457MG

    View details for PubMedID 27027962

  • Successful immunotherapy induces previously unidentified allergen-specific CD4+ T-cell subsets. Proceedings of the National Academy of Sciences of the United States of America Ryan, J. F., Hovde, R., Glanville, J., Lyu, S., Ji, X., Gupta, S., Tibshirani, R. J., Jay, D. C., Boyd, S. D., Chinthrajah, R. S., Davis, M. M., Galli, S. J., Maecker, H. T., Nadeau, K. C. 2016; 113 (9): E1286-95

    Abstract

    Allergen immunotherapy can desensitize even subjects with potentially lethal allergies, but the changes induced in T cells that underpin successful immunotherapy remain poorly understood. In a cohort of peanut-allergic participants, we used allergen-specific T-cell sorting and single-cell gene expression to trace the transcriptional "roadmap" of individual CD4+ T cells throughout immunotherapy. We found that successful immunotherapy induces allergen-specific CD4+ T cells to expand and shift toward an "anergic" Th2 T-cell phenotype largely absent in both pretreatment participants and healthy controls. These findings show that sustained success, even after immunotherapy is withdrawn, is associated with the induction, expansion, and maintenance of immunotherapy-specific memory and naive T-cell phenotypes as early as 3 mo into immunotherapy. These results suggest an approach for immune monitoring participants undergoing immunotherapy to predict the success of future treatment and could have implications for immunotherapy targets in other diseases like cancer, autoimmune disease, and transplantation.

    View details for DOI 10.1073/pnas.1520180113

    View details for PubMedID 26811452

  • Diagnosis of Food Allergy PEDIATRIC CLINICS OF NORTH AMERICA Chinthrajah, R. S., Tupa, D., Prince, B. T., Block, W. M., Rosa, J. S., Singh, A. M., Nadeau, K. 2015; 62 (6): 1393-?

    Abstract

    The prevalence of food allergies has been on the increase over the last 2 decades. Diagnosing food allergies can be complicated, as there are multiple types that have distinct clinical and immunologic features. Food allergies are broadly classified into immunoglobulin E (IgE)-mediated, non-IgE-mediated, or mixed food allergic reactions. This review focuses on the clinical manifestations of the different categories of food allergies and the different tests available to guide the clinician toward an accurate diagnosis.

    View details for DOI 10.1016/j.pcl.2015.07.009

    View details for Web of Science ID 000364106500005

    View details for PubMedID 26456439

    View details for PubMedCentralID PMC5316471

  • Oral immunotherapy for the treatment of food allergy HUMAN VACCINES & IMMUNOTHERAPEUTICS Begin, P., Chinthrajah, R. S., Nadeau, K. C. 2014; 10 (8): 2295-2302

    Abstract

    Oral immunotherapy (OIT) is an emerging new therapy for food allergy. With multiple small exploratory trials and some large randomized-controlled phase 2 trials recently published and under way, there is a clear progress and interest toward making this a treatment option for patients suffering from food allergies. However, there are still many questions to be answered and parameters to fine-tune before OIT becomes an accepted option outside of the research setting. This review covers the main milestones in the development of OIT for food allergy and further discusses important specific issues that will have direct impact on its clinical application. More specifically, previous publications showing evidence for the induction of tolerance are specifically reviewed and varying safety, tolerability and efficacy parameters from previous reports are also discussed.

    View details for DOI 10.4161/hv.29233

    View details for Web of Science ID 000344318300027

    View details for PubMedID 25424935