Changes in IgE and IgG4 epitopes of the peanut allergens following peanut oral immunotherapy

Authors: RAMBO, IAN - Oak Ridge Institute For Science And Education (ORISE); Rivers, Adam; McBride, Jane; SWIENTONIEWSKI, LAUREN - Oak Ridge Institute For Science And Education (ORISE); Cheng, Hsiaopo; SIMON, REYNA - Aimmune Therapeutics; ROBERT, RYAN - Aimmune Therapeutics; Nesbit, Jacqueline; Maleki, Soheila

Submitted to: American Academy of Allergy Asthma and Immunology
Publication Type: Abstract Only
Publication Acceptance Date: 10/30/2022
Publication Date: 2/3/2023
Citation: Rambo, I.M., Rivers, A.R., Mcbride, J.K., Swientoniewski, L., Cheng, H., Simon, R.J., Robert, R., Nesbit, J.B., Maleki, S.J. 2023. Changes in IgE and IgG4 epitopes of the peanut allergens following peanut oral immunotherapy. American Academy of Allergy Asthma and Immunology. 151,p. AB33. https://doi.org/10.1016/j.jaci.2022.12.104.
DOI: https://doi.org/10.1016/j.jaci.2022.12.104

Interpretive Summary: Peanut allergy is an often life-threatening condition that is becoming more common in developed western countries, and there is a growing need to develop effective and safe treatments. One such treatment, known as oral immunotherapy (OIT), involves eating small doses of peanuts and increasing the amount over time. This trains the body to be less sensitive and not have an allergic reaction when it encounters proteins in the peanut. Certain pieces of peanut proteins cause allergic reactions when they interact with the body's immune system, but it isn't certain which pieces are the main culprits. USDA scientists partnered with Aimmune Therapeutics to identify which protein pieces can be used to determine if a person is allergic to peanuts. By testing patient blood against hundreds of peanut protein pieces, they were able to determine which pieces created the greatest immune response before and after someone went through OIT. This presents an exciting step in determining the underlying causes of an individual's peanut allergy, as well as which protein pieces tell us if someone is now tolerant of peanuts after therapy.

Technical Abstract: Rationale:Oral immunotherapy (OIT) with Peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) is a promising treatment to desensitize peanut allergic patients. Our aim was to assess changes in IgE and IgG4 binding to peanut allergens and their epitopes recognized by peanut allergic patients undergoing OIT with PTAH in the US. Methods:Microarray slides containing synthetic overlapping 15-mer peptides of peanut allergens, Ara h 1-11, were incubated with sera from 53 peanut allergic participants from the US enrolled in Phase 2 (NCT02198664) and Phase 3 (NCT02635776) OIT studies examining PTAH vs placebo. The pre- and post- trial sera were collected 7 months to a year apart and tested for IgE and IgG4 binding to the linear peptides. ISAC arrays were conducted to detect IgE binding to the whole proteins. Results:Preliminary IgE and IgG4 epitope maps for the 11 peanut allergens were developed. While IgE binding patterns to the major epitopes for each allergen did not seem to change much, there were significant changes to the IgE binding to the intact allergens and IgE/IgG4 binding ratios of some epitopes following OIT. Conclusions: These results demonstrated that OIT with PTAH induces a shift in the intensity of IgE and IgG4 peptide binding in peanut allergic sera. While it does not seem to alter the actual peptide binding patterns significantly after one year of treatment, the antibody binding ratios and intensity are altered. This type of knowledge can be useful in the identification of peptide biomarkers that may indicate desensitization or tolerance of allergic individuals to peanut.