IgE and IgG4 epitopes of the peanut allergens shift following oral immunotherapy

Authors: RAMBO, IAN - Oak Ridge Institute For Science And Education (ORISE); KRONFEL, CHRISTINA - Oak Ridge Institute For Science And Education (ORISE); Rivers, Adam; SWIENTONIEWSKI, LAUREN - Oak Ridge Institute For Science And Education (ORISE); McBride, Jane; Cheng, Hsiaopo; SIMON, REYNA - Aimmune Therapeutics; RYAN, ROBERT - Aimmune Therapeutics; TILLES, STEPHEN - Aimmune Therapeutics; NESBIT, JACQUELINE - Oak Ridge Institute For Science And Education (ORISE); KULIS, MICHAL - University Of North Carolina; Hurlburt, Barry; Maleki, Soheila

Submitted to: Frontiers in Allergy
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/30/2023
Publication Date: 11/29/2023
Citation: Rambo, I., Kronfel, C.M., Rivers, A.R., Swientoniewski, L., Mcbride, J.K., Cheng, H., Simon, R.J., Ryan, R., Tilles, S., Nesbit, J.B., Kulis, M.D., Hurlburt, B.K., Maleki, S.J. 2023. IgE and IgG4 epitopes of the peanut allergens shift following oral immunotherapy. Frontiers in Allergy. 4: Article 1279290. https://doi.org/10.3389/falgy.2023.1279290.
DOI: https://doi.org/10.3389/falgy.2023.1279290

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. This study identifies 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: Oral immunotherapy (OIT) with peanut (Arachis hypogaea) allergen powder-dnfp (PTAH; PALFORZIA®, Aimmune Therapeutics) is a promising treatment to desensitize peanut allergic patients. Here we assessed shifts in IgE and IgG4 binding to peanut allergens and their epitopes recognized by United States (US) peanut allergic patients (n = 20) enrolled in Phase 3 (NCT02635776) OIT studies examining PTAH vs placebo. Pre- and post- trial patient sera were collected 7-12 months apart and tested for IgE binding to intact peanut proteins via ISAC immunoassays, in addition to being utilized for developing IgE and IgG4 epitope maps based on binding to synthetic overlapping 15-mer linear peptides of peanut allergens Ara h 1-11 on microarray slides. Significant IgE decreases were identified for intact Ara h 2, 3, and 6, and IgE and IgG4 linear epitope maps were developed for the 10 peanut allergens analyzed. Known and newly-identified IgE epitopes were shown to exhibit shifts towards IgG4 binding post-OIT, with the majority of linear peptides having increased IgG4 binding after treatment with PTAH. While PTAH 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.