Clinical Focus

  • Allergy and Immunology

Academic Appointments

Professional Education

  • Board Certification: American Board of Pediatrics, Pediatrics (2014)
  • Fellowship: Childrens Hospital of Philadelphia Allergy Fellowship (2016) PA
  • Board Certification: American Board of Allergy and Immunology, Allergy and Immunology (2016)
  • Residency: Childrens Hospital at Montefiore Pediatric Residency (2013) NY
  • Medical Education: SUNY Downstate College of Medicine (2010) NY

Clinical Trials

  • Prescreening Protocol to Enroll in Food Allergy Clinical Studies at a Single Site Recruiting

    This is a protocol for prescreening of participants who would like to be in clinical studies in our Center at Stanford.

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  • Effect of Different Skin Creams on TEWL Not Recruiting

    Prospective, single center, clinical pilot study to test the hypothesis that lipid rich EpiCeram® is superior in improving skin barrier function compared to Aveeno Daily Moisturising Sheer Hydration Lotion®.

    Stanford is currently not accepting patients for this trial.

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  • Follow-up of the EPITOPE Study to Evaluate Long-term Efficacy and Safety of DBV712 in Young Children Not Recruiting

    Open-label, follow-up study for subjects who completed the EPITOPE study.

    Stanford is currently not accepting patients for this trial.

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  • Food Allergen OIT for Shrimp and Cashew Not Recruiting

    A prospective Phase 2, single-center, single-allergen OIT of cashew or shrimp in participants with proven allergies to either cashew or shrimp, respectively. We intend to treat 72 participants, ages 7 to 55 years with an allergy to either cashew, or shrimp determined by Double Blind-Placebo Controlled-Food Challenge (DBPCFC), allergy history, clinical symptoms, food-allergen (FA)-specific IgE levels, and skin prick test (SPT).

    Stanford is currently not accepting patients for this trial.

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  • Peanut Oral Immunotherapy Study of Early Intervention for Desensitization Not Recruiting

    The purpose of this study is to determine the efficacy and safety of AR101 in peanut-allergic children aged 1 to \< 4 years.

    Stanford is currently not accepting patients for this trial.

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  • Safety and Efficacy Study of Viaskin Peanut in Peanut-allergic Young Children 1-3 Years of Age Not Recruiting

    The study aims to assess the safety and efficacy of Viaskin Peanut to induce desensitization to peanut in peanut-allergic children 1 to 3 years of age after a 12-month treatment by EPicutaneous ImmunoTherapy (EPIT).

    Stanford is currently not accepting patients for this trial. For more information, please contact Sayantani Sindher, 650-724-0293.

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  • Seal, Stopping Eczema and Allergy Study Not Recruiting

    This is a randomized, controlled trial designed for children who are have already developed atopic dermatitis (AD or eczema) by 12 weeks of age. The aim is to compare the effect of proactive sequential skin care, including the twice-daily use of a tri-lipid skin barrier cream (Epiceram) and proactive use of fluticasone propionate cream, against reactive AD therapy, to reduce the occurrence and severity of AD in early infancy and thereby prevent food allergy (FA).

    Stanford is currently not accepting patients for this trial. For more information, please contact Kari Nadeau, M.D., PhD, 650-724-0293.

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  • Study to Determine the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients With Eosinophilic Esophagitis (EoE) Not Recruiting

    The primary objectives of the study by study part are: Part A: To determine the treatment effect of dupilumab compared with placebo in adult and adolescent patients with EoE after 24 weeks of treatment as assessed by histological and clinical measures and to inform/confirm the final sample size determination for Part B. Part B: To demonstrate the efficacy of dupilumab treatment compared with placebo in adult and adolescent patients with EoE after 24 weeks of treatment as assessed by histological and clinical measures. Part C: To assess the safety and efficacy of dupilumab treatment in adult and adolescent patients with EoE after up to 52 weeks of treatment as assessed by histological and clinical measures. The secondary objectives of the study are: * To evaluate the safety, tolerability, and immunogenicity of dupilumab treatment for up to 52 weeks in adult and adolescent patients with EoE * To explore the relationship between dupilumab concentration and responses in adult and adolescent patients with EoE, using descriptive analyses * To evaluate the effects of dupilumab on transcriptomic signatures associated with EoE and type 2 inflammation * To demonstrate the efficacy of dupilumab treatment compared to placebo after 24 weeks and 52 weeks of treatment in adult and adolescent patients with EoE who have previously received swallowed topical corticosteroids

    Stanford is currently not accepting patients for this trial.

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Graduate and Fellowship Programs

  • Allergy/Immunology (Fellowship Program)

All Publications

  • 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


    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

  • Early intervention and prevention of allergic diseases. Allergy Brough, H. A., Lanser, B. J., Sindher, S. B., Teng, J. M., Leung, D. Y., Venter, C., Chan, S. M., Santos, A. F., Bahnson, H., Guttman-Yassky, E., Gupta, R. S., Lack, G., Ciaccio, C., Sampath, V., Nadeau, K. C., Nagler, C. R. 2021


    Food Allergy (FA) is now one of the most common chronic diseases of childhood often lasting throughout life and leading to significant worldwide healthcare burden. The precise mechanisms responsible for the development of this inflammatory condition are largely unknown; however, a multifactorial aetiology involving both environmental and genetic contributions is well accepted. A precise understanding of the pathogenesis of FA is an essential first step to developing comprehensive prevention strategies that could mitigate this epidemic. As it is frequently preceded by atopic dermatitis and can be prevented by early antigen introduction, the development of FA is likely facilitated by the improper initial presentation of antigen to the developing immune system. Primary oral exposure of antigens allowing for presentation via a well-developed mucosal immune system, rather than through a disrupted skin epidermal barrier, is essential to prevent FA. In this review, we present the data supporting the necessity of 1) an intact epidermal barrier to prevent epicutaneous antigen presentation, 2) the presence of specific commensal bacteria to maintain an intact mucosal immune system and 3) maternal/infant diet diversity, including vitamins and minerals, and appropriately timed allergenic food introduction to prevent FA.

    View details for DOI 10.1111/all.15006

    View details for PubMedID 34255344

  • 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


    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

  • 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


    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

  • Asthma phenotypes, associated comorbidities, and long-term symptoms in COVID-19 European Journal of Allergy and Clinical Immunology Eggert, L. E., He, Z., Collins, W., Lee, A. S., Nadeau, K., Chinthrajah, R. 2021

    View details for DOI 10.1111/all.14972

  • 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


    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

  • Increases in plasma IgG4/IgE with trilipid vs paraffin/petrolatum-based emollients for dry skin/eczema. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology Sindher, S., Alkotob, S. S., Shojinaga, M. N., Hamilton, R., Chan, S., Cao, S., Bahnson, H. T., Brough, H. A., Lack, G., Leung, D. Y., Nadeau, K. C. 2020

    View details for DOI 10.1111/pai.13253

    View details for PubMedID 32372469

  • Pilot study measuring transepidermal water loss (TEWL) in children suggests trilipid cream is more effective than a paraffin-based emollient. Allergy Sindher, S., Alkotob, S. S., Shojinaga, M. N., Brough, H. A., Bahnson, T., S, C., Lack, G., Leung, D. Y., Nadeau, K. C. 2020

    View details for DOI 10.1111/all.14275

    View details for PubMedID 32176320

  • 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


    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

  • Epicutaneous sensitization in the development of food allergy: What is the evidence and how can this be prevented? Allergy Brough, H. A., Nadeau, K. C., Sindher, S. B., Alkotob, S. S., Chan, S. n., Bahnson, H. n., Leung, D. Y., Lack, G. n. 2020


    There is increasing evidence regarding the importance of allergic sensitization through the skin. In this review, we provide an overview of the atopic march and immune mechanism underlying the sensitization and effector phase of food allergy. We present experimental models and human data that support the concept of epicutaneous sensitization and how this forms one half of the dual-allergen exposure hypothesis. We discuss specific important elements in the skin (FLG and other skin barrier gene mutations, Langerhans cells, type 2 innate lymphoid cells, IL-33, TSLP) that have important roles in the development of allergic responses as well as the body of evidence on environmental allergen exposure and how this can sensitize an individual. Given the link between skin barrier impairment, atopic dermatitis, food allergy, allergic asthma, and allergic rhinitis, it is logical that restoring the skin barrier and prevention or treating atopic dermatitis would have beneficial effects on prevention of related allergic diseases, particularly food allergy. We present the experimental and human studies that have evaluated this approach and discuss various factors which may influence the success of these approaches, such as the type of emollient chosen for the intervention, the role of managing skin inflammation, and differences between primary and secondary prevention of atopic dermatitis to achieve the desired outcome.

    View details for DOI 10.1111/all.14304

    View details for PubMedID 32249942

  • 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


    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. no: NCT02103270.

    View details for DOI 10.1016/j.cgh.2020.05.019

    View details for PubMedID 32434067

  • Consensus on DEfinition of Food Allergy SEverity (DEFASE): Protocol for a systematic review. The World Allergy Organization journal Arasi, S. n., Nurmatov, U. n., Turner, P. J., Ansotegui, I. J., Daher, S. n., Dunn-Galvin, A. n., Ebisawa, M. n., Eigenmann, P. n., Fernandez-Rivas, M. n., Gupta, R. n., Nowak-Wegrzyn, A. n., Petrou, S. n., Roberts, G. n., Sánchez Borges, M. A., Sindher, S. B., Tanno, L. K., Vazquez-Ortiz, M. n., Vickery, B. P., Wong, G. W., Fiocchi, A. n. 2020; 13 (12): 100493


    The term "Food Allergy" refers to a complex global health problem with a wide spectrum of severity. However, a uniform definition of severe food allergy is currently missing. This systematic review is the preliminary step towards a state-of-the-art synopsis of the current evidence relating to the severity of IgE-mediated food allergy; it will inform attempts to develop a consensus to define food allergy severity by clinicians and other stakeholders.We will undertake a systematic review, which will involve searching international biomedical databases for published studies. Studies will be independently screened against pre-defined eligibility criteria and critically appraised by established instruments. Data will be descriptively and, if possible and applicable, quantitatively synthesised.This study does not require any specific ethical approval since it is a systematic review. We plan to report results from this systematic review in a peer reviewed journal. These results will be used to inform the development of an international consensus to define severe food allergy. Author's potential conflicts of interest are clearly stated.CRD42020183103.

    View details for DOI 10.1016/j.waojou.2020.100493

    View details for PubMedID 33376574

    View details for PubMedCentralID PMC7753945

  • 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


    [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

  • 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)


    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 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

  • Can food allergy be cured? What are the future prospects? Allergy Sampath, V. n., Sindher, S. B., Alvarez Pinzon, A. M., Nadeau, K. C. 2019


    Food allergies have become a significant heath burden as prevalence continues to rise, affecting 6-13% of the global population. In the absence of drugs approved by regulatory agencies, the current standard of care remains avoidance of allergenic foods and management of acute allergic reactions with antihistamines and epinephrine auto-injectors. Allergen immunotherapy has been shown to increase the threshold of reactivity in the majority of food-allergic individuals. However, challenges include long treatment periods, high rates of adverse reactions, and lack of permanence of desensitization and established protocols. To address these limitations, adjunctive allergen-specific immunotherapy, vaccines, and non-allergen specific therapies (e.g., monoclonal antibodies) are being explored. The future of food allergy treatment is promising with a number of clinical trials in progress. Currently, although desensitization can be achieved for the majority of individuals with food allergy through immunotherapy, continued ingestion of allergen is needed for most individuals to maintain desensitization. Further understanding of the mechanisms of food allergy and identification of biomarkers to distinguish between temporary and permanent resolution of allergies is needed before a cure, where reactivity to the allergen is permanently lost enabling the individual to consume the allergen in any amount at any time, can be envisioned.

    View details for DOI 10.1111/all.14116

    View details for PubMedID 31733120

  • 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

  • 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. 2018; 9
  • 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


    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

  • The Use of Biomarkers to Predict Aero-Allergen and Food Immunotherapy Responses CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY Sindher, S. B., Long, A., Acharya, S., Sampath, V., Nadeau, K. C. 2018; 55 (2): 190–204
  • Eliciting Dose and Safety Outcomes From a Large Dataset of Standardized Multiple Food Challenges FRONTIERS IN IMMUNOLOGY Purington, N., Chinthrajah, R., 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
  • 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


    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;

    View details for DOI 10.3389/fimmu.2018.02057

    View details for PubMedID 30298065

    View details for PubMedCentralID PMC6160556

  • Comparison of sublingual immunotherapy and oral immunotherapy in peanut allergy ALLERGO JOURNAL Zhang, W., Sindher, S. B., Sampath, V., Nadeau, K. 2018; 27 (6): 22–30
  • Comparison of sublingual immunotherapy and oral immunotherapy in peanut allergy. Allergo journal international Zhang, W., Sindher, S. B., Sampath, V., Nadeau, K. 2018; 27 (6): 153-161


    The prevalence of food allergy has been increasing over the past few decades at an alarming rate with peanut allergy affecting about 2% of children. Both oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) have shown promise as a treatment option for peanut allergy. Immunotherapy induces desensitization and reduces the risk of reaction during accidental ingestion and may also enable those who are successfully desensitized to include the food allergen in their diet. OIT has been very well studied and has been found to be more efficacious that SLIT with an acceptable safety profile. However, SLIT is associated with fewer side effects. Studies indicate that a combination of SLIT and OIT may together induce a significant increase in challenge thresholds with fewer adverse events. More head-to-head clinical trials that direct compare OIT and SLIT as well as SLIT and OIT combination studies are warranted.

    View details for DOI 10.1007/s40629-018-0067-x

    View details for PubMedID 31440440

    View details for PubMedCentralID PMC6705598

  • Efficacy and safety of omalizumab in pediatric patients with high immunoglobulin E levels: A case series ALLERGY AND ASTHMA PROCEEDINGS Wang, K. Y., Sindher, S. B., Stinson, R., DaVeiga, S. 2018; 39 (4): 289–91
  • Efficacy and safety of omalizumab in pediatric patients with high immunoglobulin E levels: A case series. Allergy and asthma proceedings Wang, K. Y., Sindher, S. B., Stinson, R., DaVeiga, S. P. 2018; 39 (4): 289-291


    The efficacy and safety of omalizumab has been demonstrated in children as young as 6 years of age. Omalizumab is currently approved for a range of immunoglobulin E (IgE) levels that differ by age. In patients with IgE levels higher than the indicated therapeutic window, only a few studies have demonstrated the efficacy and safety of its use. Specifically, no reported studies exist to describe the use of omalizumab in pediatric patients with asthma ages <12 years and with high IgE levels.We reported a series of pediatric patients who were initiated on omalizumab despite an IgE level higher than the age-indicated therapeutic windows and aimed to describe whether omalizumab was safe and improved asthma outcomes.Patients who initiated omalizumab in our pediatric allergy clinic between January 2008 and December 2015, with serum IgE levels higher than the age-indicated therapeutic ranges were included. Patient charts were reviewed to determine the number of asthma-related events in the 12 months before and after initiation of omalizumab and the Asthma Control Test™ scores at the time of initiation and at 12 months of therapy.Eleven patients were identified with pretreatment IgE levels higher than the age-approved thresholds. Five patients were ages <12 years, and six patients were ages >12 years. For all but one patient, the maximum recommended dose of 375 mg every 2 weeks was effective in reducing the need for corticosteroids, emergency department visits, or hospitalizations in the year after initiation of therapy. During the period of therapy, there were no reports of severe reactions.Despite a small study group, our results indicated that omalizumab may be safely used in pediatric patients with IgE levels higher than the indicated therapeutic windows.

    View details for DOI 10.2500/aap.2018.39.4146

    View details for PubMedID 30095394

  • New treatment directions in food allergy ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY Sampath, V., Sindher, S. B., Zhang, W., Nadeau, K. C. 2018; 120 (3): 254–62

    View details for PubMedID 29508712

  • The Use of Biomarkers to Predict Aero-Allergen and Food Immunotherapy Responses. Clinical reviews in allergy & immunology Sindher, S. B., Long, A., Acharya, S., Sampath, V., Nadeau, K. C. 2018


    The incidence of allergic conditions has continued to rise over the past several decades, with a growing body of research dedicated toward the treatment of such conditions. By driving a complex range of changes in the underlying immune response, immunotherapy is the only therapy that modulates the immune system with long-term effects and is presently utilized for the treatment of several atopic conditions. Recent efforts have focused on identifying biomarkers associated with these changes that may be of use in predicting patients with the highest likelihood of positive clinical outcomes during allergen immunotherapy (AIT), providing guidance regarding AIT discontinuation, and predicting symptomatic relapse and the need for booster AIT after therapy. The identification of such biomarkers in food allergy has the additional benefit of replacing oral food challenges, which are presently the gold standard for diagnosing food allergies. While several markers have shown early promise, research has yet to identify a marker that can invariably predict clinical response to AIT. Skin prick testing (SPT) and specific IgE have commonly been used as inclusion criteria for the initiation of AIT and prediction of reactions during subsequent allergen challenge; however, existing data suggests that changes in these markers are not always associated with clinical improvement and can be widely variable, reducing their utility in predicting clinical response. Similar findings have been described for the use of allergen-specific functional IgG4 antibodies, basophil activation and histamine release, and type 2 innate lymphoid cells. There appears to be a promising association between changes in the expression of dendritic cell-associated markers, as well as the use of DNA promoter region methylation patterns in the prediction of allergy status following therapy. The cellular and molecular changes brought about by immunotherapy are still under investigation, but major strides in our understanding are being made.

    View details for PubMedID 29455358

  • New biologics for food allergy. Current opinion in allergy and clinical immunology Schuetz, J. P., Anderson, B., Sindher, S. B. 2024


    This review aims to explore role of emerging biologics, including ligelizumab, UB-221, dupilumab, and antialarmins, in food allergy management. With a focus on recent developments, we evaluate their promise in mitigating adverse events during oral immunotherapy (OIT), reducing allergic reactions, and addressing the limitations of current therapeutic options.Antiimmunoglobulin E mAbs, exemplified by omalizumab, demonstrate efficacy in desensitization and safety improvement during multiallergen OIT. Next-generation antibodies like ligelizumab and UB-221 exhibit enhanced potency and unique mechanisms, holding promise for food allergy treatment. Dupilumab, targeting IL-4 receptor alpha, presents potential benefits in decreasing allergen-specific IgE and modifying the atopic march. Exploration of antialarmins, specifically anti-IL-33 (etokimab) and anti-TSLP (tezepelumab), reveals encouraging results, with etokimab showing early success in peanut allergy trials.Biologics hold promising potential for food allergy treatment. Tailoring therapeutic approaches based on shared decision-making becomes pivotal. While omalizumab remains a significant option, next-generation anti-IgE antibodies and agents targeting alarmins exhibit unique strengths. Dupilumab, despite limited success as monotherapy, shows promise as an adjunct for OIT. Careful consideration of treatment goals, patient preferences, and the evolving landscape of biologics will shape future clinical practice, offering allergists an expanded toolbox for personalized food allergy management.

    View details for DOI 10.1097/ACI.0000000000000981

    View details for PubMedID 38547423

  • Preparing Patients for Oral Immunotherapy (PPOINT): International Delphi consensus for procedural preparation and consent. The Journal of allergy and clinical immunology Mack, D. P., Dribin, T. E., Turner, P. J., Wasserman, R. L., Hanna, M. A., Shaker, M., Tang, M. L., Rodríguez Del Río, P., Sobolewski, B., Abrams, E. M., Anagnostou, A., Arasi, S., Bajowala, S., Bégin, P., Cameron, S. B., Chan, E. S., Chinthrajah, S., Clark, A. T., Detjen, P., du Toit, G., Ebisawa, M., Elizur, A., Factor, J. M., Greiwe, J., O'B Hourihane, J., Hughes, S. W., Jones, D. H., Muraro, A., Nowak-Wegrzyn, A., Patel, N. B., Scurlock, A. M., Shah, A. N., Sindher, S. B., Tilles, S., Vickery, B. P., Wang, J., Windom, H. H., Greenhawt, M. 2024


    Despite the promise of oral immunotherapy (OIT) to treat food allergies, this procedure is associated with potential risk. There is no current agreement about what elements should be included in the preparatory or consent process.We developed consensus recommendations about the OIT process considerations and patient-specific factors that should be addressed before initiating OIT and developed a consensus OIT consent process and information form.We convened a 36-member Preparing Patients for Oral Immunotherapy (PPOINT) panel of allergy experts to develop a consensus OIT patient preparation, informed consent process, and framework form. Consensus for themes and statements was reached using Delphi methodology, and the consent information form was developed.The expert panel reached consensus for 4 themes and 103 statements specific to OIT preparatory procedures, of which 76 statements reached consensus for inclusion specific to the following themes: general considerations for counseling patients about OIT; patient- and family-specific factors that should be addressed before initiating OIT and during OIT; indications for initiating OIT; and potential contraindications and precautions for OIT. The panel reached consensus on 9 OIT consent form themes: benefits, risks, outcomes, alternatives, risk mitigation, difficulties/challenges, discontinuation, office policies, and long-term management. From these themes, 219 statements were proposed, of which 189 reached consensus, and 71 were included on the consent information form.We developed consensus recommendations to prepare and counsel patients for safe and effective OIT in clinical practice with evidence-based risk mitigation. Adoption of these recommendations may help standardize clinical care and improve patient outcomes and quality of life.

    View details for DOI 10.1016/j.jaci.2024.02.019

    View details for PubMedID 38597862

  • Varying Doses of Epicutaneous Immunotherapy With Viaskin Milk vs Placebo in Children With Cow's Milk Allergy: A Randomized Clinical Trial. JAMA pediatrics Petroni, D., Begin, P., Bird, J. A., Brown-Whitehorn, T., Chong, H. J., Fleischer, D. M., Gagnon, R., Jones, S. M., Leonard, S., Makhija, M. M., Oriel, R. C., Shreffler, W. G., Sindher, S. B., Sussman, G. L., Yang, W. H., Bee, K. J., Bois, T., Campbell, D. E., Green, T. D., Rutault, K., Sampson, H. A., Wood, R. A. 2024


    Importance: No approved treatment exists for allergen-specific immunoglobulin E (IgE)-mediated cow's milk allergy (CMA), a common childhood food allergy.Objective: To assess dose, efficacy, and safety of epicutaneous immunotherapy with Viaskin milk in children with IgE-mediated CMA.Design, Setting, and Participants: A phase 1/2, 2-part, randomized, double-blind, placebo-controlled dose-ranging clinical trial in children aged 2 to 17 years with IgE-mediated CMA was conducted between November 2014 through December 2017. It took place at 17 trial sites in the US and Canada. Current CMA was confirmed by double-blind, placebo-controlled food challenge at study entry. Part A assessed the short-term safety of 150 mug, 300 mug, or 500 mug of Viaskin milk; part B evaluated the efficacy and safety of the 3 doses vs placebo over 12 months of treatment. Of the 308 screened participants with physician-diagnosed CMA, 198 met eligibility criteria (including an eliciting dose 300 mg or less) and were randomized.Intervention: Safety of Viaskin milk (150-mug, 300-mug, or 500-mug doses) was evaluated over a 3-week period (part A). In part B, 180 additional participants were randomized to receive Viaskin milk at doses of 150 mug, 300 mug, or 500 mug or placebo (1:1:1:1) for 12 months.Main Outcomes and Measures: The primary outcome was the proportion of treatment responders, defined as a 10-fold or more increase in the cumulative reactive dose of cow's milk protein (reaching at least 144 mg) or a cumulative reactive dose of cow's milk protein at 1444 mg or more at the month 12 double-blind, placebo-controlled food challenge.Results: A total of 95.5% of the randomized participants (mean [SD] age, 8 [4.17] years; 124 of 198 were male [62.6%]) completed treatment. The highest response rate was observed in participants who received Viaskin milk at the 300-mug dose with 24 of 49 responders (49.0%) overall vs 16 of 53 responders (30.2%) in the placebo group (odds ratio, 2.19; 95% CI, 0.91-5.41; P=.09), highest in the 2 to 11 years age group (22 of 38 [57.9%] vs 13 of 40 [32.5%]; P=.04). Most treatment-emergent adverse events were mild or moderate application-site reactions. One participant in the 500-mug Viaskin milk dose group experienced treatment-related anaphylaxis.Conclusions and Relevance: In this randomized clinical trial, 12 months of daily epicutaneous immunotherapy with a dose of Viaskin milk at 300 mug was associated with a statistically significant treatment response in 2- to 11-year-old children with IgE-mediated CMA. Treatment-related anaphylaxis and treatment-related discontinuation rates were low. Further research is needed to explore Viaskin milk as a viable treatment option for children with IgE-mediated CMA.Trial Registration: Identifier: NCT02223182.

    View details for DOI 10.1001/jamapediatrics.2023.6630

    View details for PubMedID 38407859

  • Omalizumab for the Treatment of Multiple Food Allergies. The New England journal of medicine Wood, R. A., Togias, A., Sicherer, S. H., Shreffler, W. G., Kim, E. H., Jones, S. M., Leung, D. Y., Vickery, B. P., Bird, J. A., Spergel, J. M., Iqbal, A., Olsson, J., Ligueros-Saylan, M., Uddin, A., Calatroni, A., Huckabee, C. M., Rogers, N. H., Yovetich, N., Dantzer, J., Mudd, K., Wang, J., Groetch, M., Pyle, D., Keet, C. A., Kulis, M., Sindher, S. B., Long, A., Scurlock, A. M., Lanser, B. J., Lee, T., Parrish, C., Brown-Whitehorn, T., Spergel, A. K., Veri, M., Hamrah, S. D., Brittain, E., Poyser, J., Wheatley, L. M., Chinthrajah, R. S. 2024


    Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy.In this trial, we assessed whether omalizumab, a monoclonal anti-IgE antibody, would be effective and safe as monotherapy in patients with multiple food allergies. Persons 1 to 55 years of age who were allergic to peanuts and at least two other trial-specified foods (cashew, milk, egg, walnut, wheat, and hazelnut) were screened. Inclusion required a reaction to a food challenge of 100 mg or less of peanut protein and 300 mg or less of the two other foods. Participants were randomly assigned, in a 2:1 ratio, to receive omalizumab or placebo administered subcutaneously (with the dose based on weight and IgE levels) every 2 to 4 weeks for 16 to 20 weeks, after which the challenges were repeated. The primary end point was ingestion of peanut protein in a single dose of 600 mg or more without dose-limiting symptoms. The three key secondary end points were the consumption of cashew, of milk, and of egg in single doses of at least 1000 mg each without dose-limiting symptoms. The first 60 participants (59 of whom were children or adolescents) who completed this first stage were enrolled in a 24-week open-label extension.Of the 462 persons who were screened, 180 underwent randomization. The analysis population consisted of the 177 children and adolescents (1 to 17 years of age). A total of 79 of the 118 participants (67%) receiving omalizumab met the primary end-point criteria, as compared with 4 of the 59 participants (7%) receiving placebo (P<0.001). Results for the key secondary end points were consistent with those of the primary end point (cashew, 41% vs. 3%; milk, 66% vs. 10%; egg, 68% vs. 0%; P<0.001 for all comparisons). Safety end points did not differ between the groups, aside from more injection-site reactions in the omalizumab group.In persons as young as 1 year of age with multiple food allergies, omalizumab treatment for 16 weeks was superior to placebo in increasing the reaction threshold for peanut and other common food allergens. (Funded by the National Institute of Allergy and Infectious Diseases and others; number, NCT03881696.).

    View details for DOI 10.1056/NEJMoa2312382

    View details for PubMedID 38407394

  • Corrigendum: Advances and potential of omics studies for understanding the development of food allergy. Frontiers in allergy Sindher, S. B., Chin, A. R., Aghaeepour, N., Prince, L., Maecker, H., Shaw, G. M., Stevenson, D., Nadeau, K. C., Snyder, M., Khatri, P., Boyd, S. D., Winn, V. D., Angst, M. S., Chinthrajah, R. S. 2024; 5: 1373485


    [This corrects the article DOI: 10.3389/falgy.2023.1149008.].

    View details for DOI 10.3389/falgy.2024.1373485

    View details for PubMedID 38464397

    View details for PubMedCentralID PMC10921899

  • Skin as the Target for Allergy Prevention and Treatment. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology Marques-Mejias, A., Bartha, I., Ciaccio, C. E., Chinthrajah, R. S., Chan, S., Hershey, G. K., Hui-Beckman, J. W., Kost, L., Lack, G., Layhadi, J. A., Leung, D. Y., Marshall, H. F., Nadeau, K. C., Radulovic, S., Rajcoomar, R., Shamji, M. H., Sindher, S., Brough, H. A. 2024


    The fact that genetic and environmental factors could trigger disruption of the epithelial barrier and subsequently initiate a Th2 inflammatory cascade conversely proposes that protecting the same barrier and promoting adequate interactions with other organs, like the gut, may be crucial for lowering the risk and preventing atopic diseases particularly, food allergies. In this review, we provide an overview of structural characteristics that support the epithelial barrier hypothesis in AD patients, including the most relevant filaggrin gene mutations, the recent discovery of the role of the transient receptor potential vanilloid 1 (TRPV1), and the role involvement of the microbiome in healthy and damaged skin. We present experimental and human studies that support the mechanisms of allergen penetration, particularly the dual allergen exposure and the outside-in, inside-out, and outside-inside-outside hypotheses. We discuss classic skin-targeted therapies for food allergy prevention, including moisturizers, steroids, and TCI, along with pioneering trials proposed to change their current use (PACI and SEAL). We provide an overview of the novel therapies that enhance the skin barrier, like probiotics and prebiotics topical application, read-through drugs, direct and indirect FLG replacement, and IL and JAK inhibitors. Lastly, we discuss the newer strategies for preventing and treating food allergies in the form of epicutaneous immunotherapy (EPIT) and the experimental use of single-dose of adeno-associated virus (AAV) vector gene immunotherapy.

    View details for DOI 10.1016/j.anai.2023.12.030

    View details for PubMedID 38253125

  • The Stress Phenotyping Framework: A multidisciplinary biobehavioral approach for assessing and therapeutically targeting maladaptive stress physiology. Stress (Amsterdam, Netherlands) Gilgoff, R., Mengelkoch, S., Elbers, J., Kotz, K., Radin, A., Pasumarthi, I., Murthy, R., Sindher, S., Burke Harris, N., Slavich, G. M. 2024; 27 (1): 2327333


    Although dysregulated stress biology is becoming increasingly recognized as a key driver of lifelong disparities in chronic disease, we presently have no validated biomarkers of toxic stress physiology; no biological, behavioral, or cognitive treatments specifically focused on normalizing toxic stress processes; and no agreed-upon guidelines for treating stress in the clinic or evaluating the efficacy of interventions that seek to reduce toxic stress and improve human functioning. We address these critical issues by (a) systematically describing key systems and mechanisms that are dysregulated by stress; (b) summarizing indicators, biomarkers, and instruments for assessing stress response systems; and (c) highlighting therapeutic approaches that can be used to normalize stress-related biopsychosocial functioning. We also present a novel multidisciplinary Stress Phenotyping Framework that can bring stress researchers and clinicians one step closer to realizing the goal of using precision medicine-based approaches to prevent and treat stress-associated health problems.

    View details for DOI 10.1080/10253890.2024.2327333

    View details for PubMedID 38711299

  • Topical steroid withdrawal and atopic dermatitis. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology Marshall, H. F., Leung, D. Y., Lack, G., Sindher, S., Ciaccio, C. E., Chan, S., Nadeau, K. C., Brough, H. A. 2023

    View details for DOI 10.1016/j.anai.2023.12.022

    View details for PubMedID 38142858

  • The Role of Biologics in the Treatment of Food Allergy. The journal of allergy and clinical immunology. In practice Sindher, S. B., Fiocchi, A., Zuberbier, T., Arasi, S., Wood, R. A., Chinthrajah, R. S. 2023


    The landscape of food allergy (FA) treatment is poised for a paradigm shift with the emergence of biologic therapies. The FDA approval of a standardized peanut Powder for oral immunotherapy (OIT) in 2020 marked a milestone, signaling a departure from allergen avoidance toward proactive treatment strategies. While OIT has been proven effective in desensitizing patients to specific allergens, there are several limitations such as lacking standardization, a long-time commitment to achieve maintenance, and adverse events. Biologics, including omalizumab, dupilumab, and anti-alarmins, have shown promise in treating various allergic diseases, including FA. These biologics target the underlying immunological pathways driving allergic reactions, offering an antigen-agnostic approach. Omalizumab (anti-IgE) has been the most studied biologic in this space and can be utilized both as an adjunct therapy with OIT or as monotherapy. Dupilumab targeting IL-4 and IL-13 also shows promise as an adjunct therapy. The emergence of anti-alarmins further broadens the spectrum of FA treatment possibilities. Biologics represent a transformative approach to FA treatment, directly addressing the underlying mechanisms. Future research should focus on patient selection criteria, personalized biomarker panels, optimal timing of intervention, and treatment durations.

    View details for DOI 10.1016/j.jaip.2023.11.032

    View details for PubMedID 38013157

  • Combining avidin with CD63 improves basophil activation test accuracy in classifying peanut allergy. Allergy Castaño, N., Chua, K., Kaushik, A., Kim, S., Cordts, S. C., Nafarzadegan, C. D., Hofmann, G. H., Seastedt, H., Schuetz, J. P., Dunham, D., Parsons, E. S., Tsai, M., Cao, S., Desai, M., Sindher, S. B., Chinthrajah, R. S., Galli, S. J., Nadeau, K. C., Tang, S. K. 2023


    Conventional basophil activation tests (BATs) measure basophil activation by the increased expression of CD63. Previously, fluorophore-labeled avidin, a positively-charged molecule, was found to bind to activated basophils, which tend to expose negatively charged granule constituents during degranulation. This study further compares avidin versus CD63 as basophil activation biomarkers in classifying peanut allergy.Seventy subjects with either a peanut allergy (N = 47), a food allergy other than peanut (N = 6), or no food allergy (N = 17) were evaluated. We conducted BATs in response to seven peanut extract (PE) concentrations (0.01-10,000 ng/mL) and four control conditions (no stimulant, anti-IgE, fMLP (N-formylmethionine-leucyl-phenylalanine), and anti-FcεRI). We measured avidin binding and CD63 expression on basophils with flow cytometry. We evaluated logistic regression and XGBoost models for peanut allergy classification and feature identification.Avidin binding was correlated with CD63 expression. Both markers discriminated between subjects with and without a peanut allergy. Although small by percentage, an avidin+ /CD63- cell subset was found in all allergic subjects tested, indicating that the combination of avidin and CD63 could allow a more comprehensive identification of activated basophils. Indeed, we obtained the best classification accuracy (97.8% sensitivity, 96.7% specificity) by combining avidin and CD63 across seven PE doses. Similar accuracy was obtained by combining PE dose of 10,000 ng/mL for avidin and PE doses of 10 and 100 ng/mL for CD63.Avidin and CD63 are reliable BAT activation markers associated with degranulation. Their combination enhances the identification of activated basophils and improves the classification accuracy of peanut allergy.

    View details for DOI 10.1111/all.15930

    View details for PubMedID 37916710

  • Recent Mechanistic Studies in Allergic Diseases. International journal of molecular sciences Sindher, S. B., Sharma, R., Yarlagadda, M., Chin, A. R., Chinthrajah, R. S. 2023; 24 (18)


    Allergic diseases, such as food allergies, asthma, and allergic rhinitis, continue to present a significant challenge for a broad cross-section of the population, despite recent advancements in their treatment and prevention [...].

    View details for DOI 10.3390/ijms241814312

    View details for PubMedID 37762615

    View details for PubMedCentralID PMC10531635

  • Neuroimmune Pathways and Allergic Disease: An Overview. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology Long, A., Ferretti-Gallon, J. J., Chin, A. R., Chinthrajah, R. S., Sindher, S. B. 2023

    View details for DOI 10.1016/j.anai.2023.06.029

    View details for PubMedID 37517658

  • Updated Guidance Regarding The Risk ofAllergic Reactions to COVID-19 Vaccines and Recommended Evaluation and Management: A GRADE Assessment, and International Consensus Approach. The Journal of allergy and clinical immunology Greenhawt, M., Dribin, T. E., Abrams, E. M., Shaker, M., Chu, D. K., Golden, D. B., Akin, C., Anagnostou, A., ALMuhizi, F., Alqurashi, W., Arkwright, P., Baldwin, J. L., Banerji, A., Begin, P., Ben-Shoshan, M., Bernstein, J., Bingeman, T. A., Bindslev-Jensen, C., Blumenthal, K., Byrne, A., Cahil, J., Cameron, S., Campbell, D., Campbell, R., Cavender, M., Chan, E. S., Chinthrajah, S., Comberiatti, P., Eastman, J. J., Ellis, A. K., Fleischer, D. M., Fox, A., Frischmeyer-Guerrerio, P. A., Gagnon, R., Garvey, L. H., Grayson, M. H., Clarisse Isabwe, G. A., Hartog, N., Hendron, D., Horner, C. C., O'B Hourihane, J., Iglesia, E., Kan, M., Kaplan, B., Katelaris, C. H., Kim, H., Kelso, J. M., Kahn, D. A., Lang, D., Ledford, D., Levin, M., Lieberman, J. A., Loh, R., Mack, D. P., Mazer, B., Mody, K., Mosnaim, G., Munblit, D., Mustafa, S. S., Nanda, A., Nathan, R., Oppenheimer, J., Otani, I. M., Park, M., Pawankar, R., Perrett, K. P., Peter, J., Phillips, E. J., Picard, M., Pitlick, M., Ramsey, A., Rasmussen, T. H., Rathkopf, M. M., Reddy, H., Robertson, K., Rodriguez Del Rio, P., Sample, S., Sheshradi, A., Shiek, J., Sindher, S. B., Spergel, J. M., Stone, C. A., Stukus, D., Tang, M. L., Tracy, J. M., Turner, P. J., Vander Leek, T. K., Wallace, D. V., Wang, J., Wasserman, S., Weldon, D., Wolfson, A. R., Worm, M., Yacoub, M. 2023


    This guidance updates 2021 GRADE recomendations regarding immediate allergic reactions following COVID-19 vaccines and addresses re-vaccinating individuals with 1st dose allergic reactions and allergy testing to determine re-vaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 re-vaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommenations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the UK, and the US formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy, and re-vaccination after a prior immediate allergic reaction. We suggest against >15-minute post-vaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest re-vaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise, in a properly equipped setting. We suggest against pre-medication, split-dosing, or special precautions because of a comorbid allergic history.

    View details for DOI 10.1016/j.jaci.2023.05.019

    View details for PubMedID 37295474

  • Addendum: 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. 2023

    View details for DOI 10.1038/s41586-023-05977-x

    View details for PubMedID 37225997

    View details for PubMedCentralID 9746816

  • Phase 3 Trial of Epicutaneous Immunotherapy in Toddlers with Peanut Allergy. The New England journal of medicine Greenhawt, M., Sindher, S. B., Wang, J., O'Sullivan, M., du Toit, G., Kim, E. H., Albright, D., Anvari, S., Arends, N., Arkwright, P. D., Begin, P., Blumchen, K., Bourrier, T., Brown-Whitehorn, T., Cassell, H., Chan, E. S., Ciaccio, C. E., Deschildre, A., Divaret-Chauveau, A., Dorris, S. L., Dorsey, M. J., Eiwegger, T., Erlewyn-Lajeunesse, M., Fleischer, D. M., Ford, L. S., Garcia-Lloret, M., Giovannini-Chami, L., Hourihane, J. O., Jay, N., Jones, S. M., Kerns, L. A., Kloepfer, K. M., Leonard, S., Lezmi, G., Lieberman, J. A., Lomas, J., Makhija, M., Parrish, C., Peake, J., Perrett, K. P., Petroni, D., Pfutzner, W., Pongracic, J. A., Quinn, P., Robison, R. G., Sanders, G., Schneider, L., Sharma, H. P., Trujillo, J., Turner, P. J., Tuttle, K., Upton, J. E., Varshney, P., Vickery, B. P., Vogelberg, C., Wainstein, B., Wood, R. A., Bee, K. J., Campbell, D. E., Green, T. D., Rouissi, R., Peillon, A., Bahnson, H. T., Bois, T., Sampson, H. A., Burks, A. W. 2023; 388 (19): 1755-1766


    BACKGROUND: No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown.METHODS: We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (thedose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. Safety was assessed according to the occurrence of adverse events during the use of the peanut patch or placebo.RESULTS: Of the 362 patients who underwent randomization, 84.8% completed the trial. The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group (risk difference, 33.4 percentage points; 95% confidence interval, 22.4 to 44.5; P<0.001). Adverse events that occurred during the use of the intervention or placebo, irrespective of relatedness, were observed in 100% of the patients in the intervention group and 99.2% in the placebo group. Serious adverse events occurred in 8.6% of the patients in the intervention group and 2.5% of those in the placebo group; anaphylaxis occurred in 7.8% and 3.4%, respectively. Serious treatment-related adverse events occurred in 0.4% of patients in the intervention group and none in the placebo group. Treatment-related anaphylaxis occurred in 1.6% in the intervention group and none in the placebo group.CONCLUSIONS: In this trial involving children 1 to 3 years of age with peanut allergy, epicutaneous immunotherapy for 12 months was superior to placebo in desensitizing children to peanuts and increasing the peanut dose that triggered allergic symptoms. (Funded by DBV Technologies; EPITOPE number, NCT03211247.).

    View details for DOI 10.1056/NEJMoa2212895

    View details for PubMedID 37163622

  • Treatment of food allergy: oral immunotherapy, biologics and beyond. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology Sindher, S. B., Hillier, C., Anderson, B., Long, A., Chinthrajah, R. S. 2023


    The prevalence of food allergy has been increasing globally, and comes with a heavy burden not just economically, but also on quality of life. Although oral immunotherapy (OIT) is effective at inducing desensitization to food allergens, it has several limitations that weaken its success. Limitations include long duration of build-up, especially if used for multiple allergens, and high rate of reported adverse events. Furthermore, OIT may not be effective in all patients. Efforts are underway to identify additional treatment options, either as monotherapy or in combination, to treat food allergy or enhance safety and efficacy of OIT. Biologics such as omalizumab and dupulimab, which already have FDA approval for other atopic conditions have been the most studied, but additional biologics and novel strategies are emerging. In this review we discuss therapeutic strategies including IgE inhibitors, IgE disruptors, IL-4 and IL-13 inhibitors, anti-alarmins, JAK1 and BTK inhibitors, and nanoparticles and the data surrounding their application in food allergy and highlight their potential.

    View details for DOI 10.1016/j.anai.2023.04.023

    View details for PubMedID 37100276

  • Food allergy risks and dining industry - an assessment and a path forward. Frontiers in allergy Stankovich, G. A., Warren, C. M., Gupta, R., Sindher, S. B., Chinthrajah, R. S., Nadeau, K. C. 2023; 4: 1060932


    Food allergies have increased in prevalence over the last few decades and continue to grow. Consumption of even trace amounts of common foods can cause a rapid allergic reaction (generally within minutes) which can be mild to severe to even life-threatening. Eating at restaurants poses a risk of allergic reactions for those with food allergies due to inadequate, inconsistent labeling of allergens in foods. Here, we review food labeling rules and practices in the restaurant industry and compare and contrast it with food labeling for prepackaged foods. We review global and United States trends, and provide a brief historical overview. The paper describes the key legal and economic motivations behind restaurant food labeling. Next, we describe novel risk-driven policies and new biotechnologies that have the potential to change food labeling practices worldwide. Finally, we outline desirable federal regulations and voluntary information disclosures that would positively impact the public health aspects of restaurant food labeling and improve the quality of life for people with severe food allergies.

    View details for DOI 10.3389/falgy.2023.1060932

    View details for PubMedID 37064717

    View details for PubMedCentralID PMC10090668

  • Advances and potential of omics studies for understanding the development of food allergy. Frontiers in allergy Sindher, S. B., Chin, A. R., Aghaeepour, N., Prince, L., Maecker, H., Shaw, G. M., Stevenson, D. K., Nadeau, K. C., Snyder, M., Khatri, P., Boyd, S. D., Winn, V. D., Angst, M. S., Chinthrajah, R. S. 2023; 4: 1149008


    The prevalence of food allergy continues to rise globally, carrying with it substantial safety, economic, and emotional burdens. Although preventative strategies do exist, the heterogeneity of allergy trajectories and clinical phenotypes has made it difficult to identify patients who would benefit from these strategies. Therefore, further studies investigating the molecular mechanisms that differentiate these trajectories are needed. Large-scale omics studies have identified key insights into the molecular mechanisms for many different diseases, however the application of these technologies to uncover the drivers of food allergy development is in its infancy. Here we review the use of omics approaches in food allergy and highlight key gaps in knowledge for applying these technologies for the characterization of food allergy development.

    View details for DOI 10.3389/falgy.2023.1149008

    View details for PubMedID 37034151

    View details for PubMedCentralID PMC10080041

  • Spheromers reveal robust T cell responses to the Pfizer/BioNTech vaccine and attenuated peripheral CD8+ T cell responses post SARS-CoV-2 infection. Immunity Gao, F., Mallajoysula, V., Arunachalam, P. S., van der Ploeg, K., Manohar, M., Röltgen, K., Yang, F., Wirz, O., Hoh, R., Haraguchi, E., Lee, J. Y., Willis, R., Ramachandiran, V., Li, J., Kathuria, K. R., Li, C., Lee, A. S., Shah, M. M., Sindher, S. B., Gonzalez, J., Altman, J. D., Wang, T. T., Boyd, S. D., Pulendran, B., Jagannathan, P., Nadeau, K. C., Davis, M. M. 2023


    T cells are a critical component of the response to SARS-CoV-2, but their kinetics after infection and vaccination are insufficiently understood. Using "spheromer" peptide-MHC multimer reagents, we analyzed healthy subjects receiving two doses of the Pfizer/BioNTech BNT162b2 vaccine. Vaccination resulted in robust spike-specific T cell responses for the dominant CD4+ (HLA-DRB1∗15:01/S191) and CD8+ (HLA-A∗02/S691) T cell epitopes. Antigen-specific CD4+ and CD8+ T cell responses were asynchronous, with the peak CD4+ T cell responses occurring 1 week post the second vaccination (boost), whereas CD8+ T cells peaked 2 weeks later. These peripheral T cell responses were elevated compared with COVID-19 patients. We also found that previous SARS-CoV-2 infection resulted in decreased CD8+ T cell activation and expansion, suggesting that previous infection can influence the T cell response to vaccination.

    View details for DOI 10.1016/j.immuni.2023.03.005

    View details for PubMedID 36996809

    View details for PubMedCentralID PMC10017386

  • The role of biologics in pediatric food allergy and eosinophilic gastrointestinal disorders. The Journal of allergy and clinical immunology Sindher, S. B., Barshow, S., Tirumalasetty, J., Arasi, S., Atkins, D., Bauer, M., Bégin, P., Collins, M. H., Deschildre, A., Doyle, A. D., Fiocchi, A., Furuta, G. T., Garcia-Lloret, M., Mennini, M., Rothenberg, M. E., Spergel, J. M., Wang, J., Wood, R. A., Wright, B. L., Zuberbier, T., Chin, A. R., Long, A., Nadeau, K. C., Chinthrajah, R. S. 2023; 151 (3): 595-606


    Continuing insight into the molecular mechanisms of atopic disorders has enabled the development of biologics to precisely target these diseases. Food allergy (FA) and eosinophilic gastrointestinal disorders (EGIDs) are driven by similar inflammatory molecular mechanisms and exist along the same atopic disease spectrum. Therefore, many of the same biologics are being investigated to target key drivers of mechanisms shared across the disease states. The enormous potential of biologics for the treatment of FA and EGIDs is highlighted by the significant increases in the number of ongoing clinical trials (more than 30) evaluating their use in these disease states, as well as by the recent US Food and Drug Administration approval of dupilumab for the treatment of eosinophilic esophagitis. Here we discuss past and current research into the use of biologics in FA and EGIDs and their potential role in improving treatment options in the future, with the need to have biologics widely clinically available.

    View details for DOI 10.1016/j.jaci.2023.01.007

    View details for PubMedID 36872039

  • Transitioning from epicutaneous to oral peanut immunotherapy. Frontiers in allergy Wong, L., Kost, L., Anderson, B., Long, A., Sindher, S. B., Chinthrajah, R. S., Collins, W. J. 2023; 4: 1089308


    Epicutaneous immunotherapy (EPIT) has been tested in clinical trials for children with peanut allergy (PA) for its safety and efficacy in inducing desensitization. Aside from peanut avoidance and symptom management, oral immunotherapy (OIT) is another option for PA patients. However, OIT can be associated with adverse events and pose safety concerns to children and their caregivers.This study assessed 27 children who successfully completed a peanut EPIT trial. 18 of them transitioned to peanut OIT with starting doses ranging from 10-600 mg of peanut protein. Our aim was to learn more about the EPIT to OIT experience through descriptive survey responses and to gather information that may support the sequential use of the two immunotherapies for safe and positive outcomes that may not be achieved by either alone.Overall, children and their caregivers had less anxiety about starting OIT after having had peanut exposure through EPIT. Most children who transitioned from EPIT to OIT had no or minor symptoms initially, with symptoms lessening later in OIT. Most were also able to maintain or increase their peanut dose over time, achieving maintenance doses of 60-2,000 mg.In comparison with current literature on OIT for PA in children, the reported symptoms appeared less severe and less prevalent in the EPIT to OIT group. However, there were 3 participants who withdrew from OIT due to the development of intolerable symptoms. This study provides initial data in support of EPIT to OIT, and larger randomized controlled trials assessing effectiveness of the two therapies together are warranted.

    View details for DOI 10.3389/falgy.2023.1089308

    View details for PubMedID 36814725

    View details for PubMedCentralID PMC9939758

  • Baseline Epitope-Specific IgE Profiles are Predictive of Sustained Unresponsiveness One Year Post OIT in the POISED Trial Lee, A., Suprun, M., Getts, R., Peck, S., Sindher, S., Nadeau, K., Chinthrajah, R., Galli, S., Sampson, H. MOSBY-ELSEVIER. 2023: AB120
  • Management of Eosinophilic Esophagitis in Pediatric Patients Undergoing Food Allergen Oral Immunotherapy Jia, X., Chin, A., Khavari, N., Haija, M., McGhee, S., Chinthrajah, S., Sindher, S. MOSBY-ELSEVIER. 2023: AB88
  • The Impact of Persistent Gastrointestinal Symptoms on Completion of Oral Immunotherapy in Clinical Trials Lim, J., Cao, S., Chinthrajah, S., Sindher, S. MOSBY-ELSEVIER. 2023: AB34
  • The Effects of Long-term Food Oral Immunotherapy on Compliance, Quality of Life, and Perceived Burden of Care Tirumalasetty, J., Sullivan, L., Martinez, K., Collins, W., Albarran, M., Gajare, P., Kost, L., Chinthrajah, S., Sindher, S., Cao, S. MOSBY-ELSEVIER. 2023: AB29
  • Asthma-Related Healthcare Resource Use And Costs In Patients With Documented Food Allergies Seetasith, A., Sindher, S., Boudreau, D., Liu, Y., Gupta, S., Ciaccio, C. MOSBY-ELSEVIER. 2023: AB186
  • Impact of OIT on Cumulative Ingested Dose across Multiple Oral Immunotherapy Trials Parsons, E., Quake, A., Seastedt, H., Cao, S., Raeber, O., Kaushik, A., Andorf, S., Manohar, M., Sharon, C., Nadeau, K., Sindher, S. MOSBY-ELSEVIER. 2023: AB36
  • Xenobiotic Metabolites Decrease Over Time During Oral Immunotherapy in Children with Multiple Food Allergies Quake, A., Parsons, E., Sanchez, J., DeFelice, B., Nadeau, K., Sindher, S. MOSBY-ELSEVIER. 2023: AB32
  • Correction: Quake et al. Early Introduction of Multi-Allergen Mixture for Prevention of Food Allergy: Pilot Study. Nutrients&amp;nbsp;2022, 14, 737. 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; 15 (1)


    In the original publication [...].

    View details for DOI 10.3390/nu15010135

    View details for PubMedID 36615910

  • Editorial comments on "Early initiation of short-term emollient use for the prevention of atopic dermatitis in high-risk infants - The STOP-AD randomized controlled trial" - is emollient therapy enough? Allergy Brough, H. A., Sindher, S., Nadeau, K. C. 2022

    View details for DOI 10.1111/all.15626

    View details for PubMedID 36573442

  • 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


    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

  • The impact of COVID-19 on a national sample of US adults with food allergy 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. 2022; 10 (10): 2744-2747
  • 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

  • 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)


    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, 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

  • 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


    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


    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

  • 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


    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)


    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
  • 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
  • Understanding the Association of IgE and Gut and Mucosal Proteins in Atopic Disorders Shah, A., Parsons, E., Smith, E., Kost, L., Ogulur, I., Heider, A., Tan, G., Hamilton, R., Sindher, S., Liu, F., Akdis, C., Lieb, R., Nadeau, K., Lejeune, S. MOSBY-ELSEVIER. 2022: AB229
  • Fish and shellfish allergy: Are they different in different countries? Nakonechna, A., van Bergen, A., Anantharachagan, A., Arnold, D., Johnston, N., Nadeau, K., Rutkowski, C., Sindher, S., Sriaroon, P., Thomas, I., Vijayadurai, P., Wagner, A. MOSBY-ELSEVIER. 2022: AB112
  • 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
  • Studies on Cashew and Shrimp-Oral Immunotherapy-Induced Changes in Allergen-Reactive CD4+T Cells Fernandes, A., Gupta, S., Cao, S., Maysel-Auslender, S., Dunham, D., Lyu, S., Sindher, S., Manohar, M., Maecker, H., Nadeau, K. MOSBY-ELSEVIER. 2022: AB40
  • 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


    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


    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, 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

  • 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


    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

  • Pediatric eosinophilic esophagitis outcomes vary with co-morbid eczema and pollen food syndrome. Frontiers in allergy Sessions, J., Purington, N., Wang, Y., McGhee, S., Sindher, S., Goyal, A., Khavari, N. 2022; 3: 981961


    Background: Eosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory disease characterized by eosinophil inflammation of the esophagus. It has been described as a component of the Allergic March and is often seen with other atopic diseases. Some atopic diseases, including asthma, are known to be heterogenous with endotypes that guide treatment. Similarly, we propose that EoE is a heterogenous disease with varying phenotypes and endotypes that might impact response to therapy.Methods: A single-center retrospective review of pediatric patients ≤18 years of age diagnosed with EoE was conducted. All gastrointestinal clinic visits and esophagogastroduodenoscopies (EGD) from disease presentation through the first three years after diagnosis were reviewed. Histologic remission rate and therapies utilized [proton pump inhibitor (PPI), topical steroid, dietary elimination] were assessed.Results: One hundred and thirty-seven patients were included, 80% of whom had at least one concurrent atopic condition at diagnosis, with food allergies being the most common (57%) followed by eczema (34%), and asthma (29%). The remission rate of the overall cohort was 65%, and by concurrent allergy, comorbid pollen food syndrome and eczema had the highest remission rates at 100% and 81%, respectively followed by asthma (62%), food allergies (62%), seasonal allergic rhinitis (60%), and history of anaphylaxis (56%). Kaplan-Meier curves for each atopic condition show that patients with eczema and pollen food syndrome achieve histologic remission faster than those without. All treatment modalities were more successful in patients with eczema than those without, and PPI was most effective treatment at inducing remission.Conclusions: In a real-world pediatric cohort, 80% of patients with EoE had an underlying atopic condition. Patients with eczema and pollen food syndrome had a swifter response and were more likely to achieve histologic remission than patients with other atopic conditions. This study suggests that EoE, like other allergic diseases, may have heterogenous phenotypes that could affect response to treatment. There is currently a knowledge gap in classifying EoE based on endotypes and phenotypes at diagnosis and correlating responses to various treatment modalities.

    View details for DOI 10.3389/falgy.2022.981961

    View details for PubMedID 36118171

  • 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


    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

  • 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


    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

  • Advances, Practical Implementation, and Unmet Needs Regarding Oral Immunotherapy for Food Allergy. The journal of allergy and clinical immunology. In practice Perrett, K. P., Sindher, S. B., Begin, P., Shanks, J., Elizur, A. 2021


    Treatment of food allergy is a rapidly changing landscape, with arguably, the most significant advancement in recent years, the transition of oral immunotherapy (OIT) to clinical practice. As an innovation, OIT is a phase of rapidly increasing demand, particularly for some allergens such as peanut, egg, and milk, which have substantial evidence of efficacy. However, significant questions remain about how to best treat multiple food allergies and less common food allergies and how to optimize long-term safety and efficacy. This review summarizes the currently available resources for integrating food allergy OIT into clinical practice and focuses on the multiple remaining unmet needs such as providing an approach for OIT to food allergens for which there is no or limited evidence; practical issues related to food allergy treatment particularly when it is not going well; long-term outcomes and follow-up after OIT; and strategies to help meet the impending increase in demand.

    View details for DOI 10.1016/j.jaip.2021.10.070

    View details for PubMedID 34785391

  • 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


    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

  • 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


    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


    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

  • Basophil activation tests identify a peanut OIT subgroup with improved safety and outcomes Chinthrajah, S., Cao, S., Tsai, M., Mukai, K., Tibshirani, R., Sindher, S., Nadeau, K., Galli, S. MOSBY-ELSEVIER. 2021: AB166
  • 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


    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