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


  • Follow-up of the EPITOPE Study to Evaluate Long-term Efficacy and Safety of DBV712 in Young Children Recruiting

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

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  • Peanut Oral Immunotherapy Study of Early Intervention for Desensitization Recruiting

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

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  • 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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  • Safety and Efficacy Study of Viaskin Peanut in Peanut-allergic Young Children 1-3 Years of Age 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).

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  • Study to Determine the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients With Eosinophilic Esophagitis (EoE) 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

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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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Graduate and Fellowship Programs


  • Allergy/Immunology (Fellowship Program)

All Publications


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

    Abstract

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

    View details for DOI 10.1016/j.jaip.2022.03.004

    View details for PubMedID 35306179

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

    Abstract

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

    View details for DOI 10.3390/nu14040737

    View details for PubMedID 35215387

  • Dose-related allergic adverse events during multi-food oral immunotherapy Gajare, P., Cao, S., Anderson, B., Lloret, M., Zedeck, S., Kost, L., Nadeau, K., Chinthrajah, S., Sindher, S., Long, A. MOSBY-ELSEVIER. 2022: AB34
  • Feasibility of Virtual Reality Technology to Improve Experience During Pediatric Oral Food Challenge Collins, W., Adlou, B., Rodriguez, A., Albarran, M., O'Neal, E., Weiss, T., Hsu, K., Sindher, S., Bailenson, J., Caruso, T., Chinthrajah, S. MOSBY-ELSEVIER. 2022: AB108
  • 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

    Abstract

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

    View details for DOI 10.1111/all.15229

    View details for PubMedID 35073410

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

    Abstract

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

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

    View details for PubMedID 35065784

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

    Abstract

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

    View details for DOI 10.1016/j.cell.2022.01.018

    View details for PubMedID 35148837

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

    Abstract

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

    View details for DOI 10.1111/all.15217

    View details for PubMedID 35014049

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

    Abstract

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

    View details for DOI 10.1016/j.jaip.2021.11.017

    View details for PubMedID 34848381

  • 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

    Abstract

    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

    Abstract

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

    View details for DOI 10.1111/pai.13679

    View details for PubMedID 34655480

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

    Abstract

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

    View details for DOI 10.1001/jamanetworkopen.2021.25524

    View details for PubMedID 34533570

  • 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

    Abstract

    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

  • Asthma phenotypes, associated comorbidities, and long-term symptoms in COVID-19. Allergy Eggert, L. E., He, Z., Collins, W., Lee, A. S., Dhondalay, G., Jiang, S. Y., Fitzpatrick, J., Snow, T. T., Pinsky, B. A., Artandi, M., Barman, L., Puri, R., Wittman, R., Ahuja, N., Blomkalns, A., O'Hara, R., Cao, S., Desai, M., Sindher, S. B., Nadeau, K., Chinthrajah, R. S. 2021

    Abstract

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

    View details for DOI 10.1111/all.14972

    View details for PubMedID 34080210

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

    Abstract

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

    View details for DOI 10.1016/j.jaip.2021.05.020

    View details for PubMedID 34089927

  • 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

    Abstract

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

    View details for DOI 10.3389/falgy.2021.779804

    View details for PubMedID 35387040

    View details for PubMedCentralID PMC8974765

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

    Abstract

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

    View details for DOI 10.1016/j.fct.2021.112125

    View details for PubMedID 33722597

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

    Abstract

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

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

    View details for PubMedID 34252919

  • 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

    Abstract

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

    View details for DOI 10.1111/all.14613

    View details for PubMedID 33020913

  • 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

    Abstract

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

    View details for DOI 10.1016/j.waojou.2020.100455

    View details for PubMedID 33005286

    View details for PubMedCentralID PMC7519204

  • 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

    Abstract

    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

    Abstract

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

    View details for DOI 10.1016/j.cgh.2020.05.019

    View details for PubMedID 32434067

  • 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

    Abstract

    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

    Abstract

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

    View details for DOI 10.3389/fimmu.2020.625796

    View details for PubMedID 33329616

    View details for PubMedCentralID PMC7734876

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

    Abstract

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

    View details for DOI 10.1172/jci.insight.131347

    View details for PubMedID 31723064

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

    View details for DOI 10.1016/j.jaci.2019.10.021

    View details for PubMedID 31678426

  • 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

    Abstract

    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

    Abstract

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

    View details for DOI 10.3389/fimmu.2018.02689

    View details for PubMedID 30538699

    View details for PubMedCentralID PMC6277531

  • 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

    Abstract

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

    View details for DOI 10.3389/fimmu.2018.02057

    View details for PubMedID 30298065

    View details for PubMedCentralID PMC6160556

  • 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

    Abstract

    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

    Abstract

    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

    Abstract

    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