Oral desensitization therapy for peanut allergy induces dynamic changes in peanut-specific immune responses

• Type of Material: Article
• Authors: Veronique Bajzik, Benaroya Research Institute; Hannah A. DeBerg, Benaroya Research Institute; Nahir Garabatos, Benaroya Research Institute; Blake J. Rust, Benaroya Research Institute; Kimberly K. Obrien, Benaroya Research Institute; Quynh-Anh Nguyen, Benaroya Research Institute; Colin O'Rourke, Benaroya Research Institute; Alex Smith, Aimmune Therapeutics; Alex H. Walker, Benaroya Research Institute; Charlie Quinn, Benaroya Research Institute; Vivian H. Gersuk, Benaroya Research Institute; Mary Farrington, Virginia Mason Medical Center; David Jeong, Virginia Mason Medical Center; Brian Vickery, Emory University; Daniel C. Adelman, University of California San Francisco; Erik Wambre, Benaroya Research Institute
• Language: English
• Date: 2022-03-14
• Publisher: WILEY
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
• Final Published Version (URL): http://dx.doi.org/10.1111/all.15276
• Title of Journal or Parent Work: ALLERGY
• Volume: 77
• Issue: 8
• Start Page: 2534
• End Page: 2548
• Grant/Funding Information: This work was supported by funds from NIH (grant R01 AI108839 and U19 AI135817 to E. Wambre). Food Allergy Research and Education (FARE) contributed supplemental support to the Wambre Laboratory. Aimmune Therapeutics provided support to the Benaroya Research Institute for experiments on samples from Aimmune’s clinical trial. The funding sources had no influence with regards to sample analysis or interpretation of data.
• Keywords: CD4(+) T-CELLS; CD63; CD203C EXPRESSION; PATHOGENESIS; IMMUNOTHERAPY; BASOPHIL ACTIVATION TEST; oral immunotherapy; EPIDEMIOLOGY; DOUBLE-BLIND; Science & Technology; Life Sciences & Biomedicine; Immunology; CD4+T cells; Allergy; DIAGNOSIS; peanut allergy; Th2A cells; FOOD ALLERGY; basophils
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Immunology

Abstract

Background: The PALISADE study, an international, phase 3 trial of peanut oral immunotherapy (POIT) with AR101, resulted in desensitization in children and adolescents who were highly allergic to peanut. An improved understanding of the immune mechanism induced in response to food allergen immunotherapy would enable more informed and effective therapeutic strategies. Our main purpose was to examine the immunological changes in blood samples from a subset of peanut-allergic individuals undergoing oral desensitization immunotherapy with AR101. Methods: Blood samples obtained as part of enrollment screening and at multiple time points during PALISADE study were used to assess basophil and CD4+ T-cell reactivity to peanut. Results: The absence of clinical reactivity to the entry double-blinded placebo-controlled peanut challenge (DBPCFC) was accompanied by a significantly lower basophil sensitivity and T-cell reactivity to peanut compared with DBPCFC reactors. At baseline, peanut-reactive TH2A cells were observed in many but not all peanut-allergic patients and their level in peripheral blood correlates with T-cell reactivity to peanut and with serum peanut-specific IgE and IgG4 levels. POIT reshaped circulating peanut-reactive T-cell responses in a subset-dependent manner. Changes in basophil and T-cell responses to peanut closely paralleled clinical benefits to AR101 therapy and resemble responses in those with lower clinical sensitivity to peanut. However, no difference in peanut-reactive Treg cell frequency was observed between groups. Conclusion: Oral desensitization therapy with AR101 leads to decreased basophil sensitivity to peanut and reshapes peanut-reactive T effector cell responses supporting its potential as an immunomodulatory therapy.