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Randomized Controlled Trial
. 2025 Mar;155(3):923-931.e2.
doi: 10.1016/j.jaci.2024.10.017. Epub 2024 Nov 5.

Baseline epitope-specific IgE profiles are predictive of sustained unresponsiveness or high threshold 1-year post oral immunotherapy in the POISED trial

Maria Suprun  1 , Ashley Sang Eun Lee  1 , Robert Getts  2 , Simon Peck  1 , Sayantani B Sindher  3 , Kari C Nadeau  3 , R Sharon Chinthrajah  3 , Stephen J Galli  4 , Hugh A Sampson  5
Affiliations
Randomized Controlled Trial

Baseline epitope-specific IgE profiles are predictive of sustained unresponsiveness or high threshold 1-year post oral immunotherapy in the POISED trial

Maria Suprun et al. J Allergy Clin Immunol. 2025 Mar.

Abstract

Background: Results from the POISED trial suggest that discontinuation of peanut oral immunotherapy can increase the risk of regaining clinical reactivity to peanut.

Objective: We sought to determine whether patients who achieved sustained unresponsiveness (SU) or sustained high threshold (SHT) have different baseline sequential epitope-specific IgE profiles than patients who achieved transient desensitization.

Methods: Subjects in the POISED trial (NCT02103270) were randomized to peanut (n = 95) or placebo (n = 25) for 24 months. Oral immunotherapy-desensitized subjects were then assigned to no peanut (PN-0) (n = 51) or 300 mg peanut (PN-300) (n = 30) for 12 months. SU and SHT were determined by subjects in PN-0 and PN-300, respectively, passing 4000-mg peanut oral challenge. Specific IgE and IgG4 levels to peanut; Ara h 1, Ara h 2, and Ara h 3 proteins; and 64 allergenic epitopes were measured. We developed machine learning models with bootstrap simulations using baseline data to predict SU/SHT.

Results: Of 80 (84%) subjects who were desensitized to peanut, 13% (n = 8) and 37% (n = 13) achieved SU/SHT in PN-0 and PN-300 groups. Decreases in epitope-and protein-specific IgE levels and increases in IgG4 levels were observed during 2 years of oral immunotherapy. At baseline, patients with SU in PN-0, but not PN-300, group had lower epitope-specific IgE and protein-specific IgE levels compared with the transient desensitization group. A machine learning model with 12 baseline epitope-specific IgEs and age could predict SU/SHT with accuracy of 94%, area under the curve 0.97, sensitivity 1.00, and specificity 0.91.

Conclusions: Subjects who achieved SU/SHT had different baseline protein- and epitope-specific IgE profiles than subjects with transient desensitization. These profiles may help identify patients with an increased likelihood of achieving SU/SHT.

Keywords: Food allergy; epitope-binding profiles; epitopes; oral immunotherapy; sustained unresponsiveness.

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Conflict of interest statement

Disclosure statement Funding was provided by the David H. and Julia Koch Research Program in Food Allergy Therapeutics (to H.A.S.), Allergenis (to H.A.S. and M.S.), National Institute of Allergy and Infectious Diseases grants U19AI104209 and R01AI140134, Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Naddisy Foundation, Sunshine Foundation, Hartman Family Foundation, and Friend Family Foundation. Disclosure of potential conflict of interest: M. Suprun is an employee at Janssen. R. Getts is an employee of Allergenis. S. B. Sindher reports grants from National Institute of Allergy and Infectious Diseases, Regeneron, DBV Technologies, Aimmune Therapeutics, Novartis, and Sanofi and personal fees from AstraZeneca. K. C. Nadeau reports grants from National Institute of Allergy and Infectious Diseases, National Heart, Lung, and Blood Institute, National Institute of Environmental Health Sciences, and Food Allergy Research & Education (FARE); other fees from World Allergy Organization, Cour Pharma; and other compensation from Before Brands, Alladapt, Latitude, IgGenix, Immune Tolerance Network, and National Institutes of Health clinical research centers. K. C. Nadeau has the following patents pending: “Inhibition of allergic reaction to peanut allergen using an IL-33 inhibitor”; “Special oral formula for decreasing food allergy risk and treatment for food allergy”; “Basophil activation based diagnostic allergy test”; “Granulocyte-based methods for detecting and monitoring immune system disorders pending”; “Methods and assays for detecting and quantifying pure subpopulations of white blood cells in immune system disorders”; “Mixed allergen compositions and methods for using the same”; “Microfluidic device and diagnostic methods for allergy testing based on detection of basophil activation.” R. S. Chinthrajah reports grants from National Institute of Allergy and Infectious Diseases, Aimmune Therapeutics, DBV Technologies, Astellas, and Regeneron and is an advisory board member for Alladapt, Genentech, Novartis, and Sanofi. S. J. Galli reports grants from National Institutes of Health/National Institute of Allergy and Infectious Diseases, including grant U19 AI104209 (which supports the POISED trial), is a scientific advisor and has a grant from Emmune, Inc, and is on the Scientific Advisory Board of Jasper Therapeutics Inc. H. A. Sampson receives funding to his institution for grants from National Institutes of Health/National Institute of Allergy and Infectious Diseases; has received consulting fees from DBV Technologies, S.A., N-Fold Therapeutics, LLC, and Siolta, Inc; and has stock options from DBV Technologies and N-Fold Therapeutics. The rest of the authors declare that they have no relevant conflicts of interest.

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