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

Background: 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. Methods: 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. Results: 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. Conclusion: 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.