Distinct Gene Expression Profiles of Ara h 2-Specific B Cells in Desensitization and Tolerance During Peanut Oral Immunotherapy.

Abstract

Peanut oral immunotherapy (OIT) is an effective way to treat peanut allergy. Patients undergoing OIT show high rates of desensitization to the triggering food items after a completed therapy. Long-term tolerance is often achieved, but the mechanism of tolerance after OIT is not well understood. In this study, we aimed to characterize the changes in allergen-specific B cell gene expression caused by peanut OIT and the effects of extended allergen avoidance after OIT. We analyzed the gene expression of Ara h 2-specific B cells from 34 peanut allergic children from the peanut OIT IMPACT trial. We labeled PBMCs using biotinylated allergen to sort and pool allergen-specific B cells for sequencing. We compared the OIT and placebo arm after 30 months of active treatment and additionally after an avoidance phase of 6 months with no allergen exposure. After OIT, there was significantly altered gene expression in allergen-specific B cells. In tolerant participants, they exhibited gene expression related to regulatory B cells, suppressed B cell activation, immune regulation, increased cell-cell communication, and antigen presentation. These tolerance-induced changes in gene expression are different from remission as the 6-month avoidance period caused some participants to lose clinical tolerance. The difference between tolerance and desensitization appeared in increased antiviral response in desensitized individuals, whereas IL-10 and TGFβ-related signaling increased in the tolerant group. Allergen-specific B cells from OIT participants display a transcriptional profile associated with clinical remission, characterized by the expression of genes previously linked to regulatory B cell function.