Diverging in Vivo Immune Response Patterns After Oral Food Challenge in Peanut Allergic Adults

Peanut (PN) allergy is an IgE-mediated hypersensitivity with a deviated adaptive immune response dominated by IgE-producing B cells and type 2 T cells (Th2). The in vivo immune response upon antigen encounter, for example, after oral food challenge (OFC), has not been investigated over prolonged timeframes.

Here, we investigated the kinetics of allergen-specific adaptive immune responses in PN-allergic and non-allergic adults before OFC (d0) and thereafter at d7, d14, d21, d28 by determining PN-specific CD40L⁺4-1BB⁺ conventional (Tconv) and FoxP3⁺ Helios⁺ CD40L^-4-1BB⁺ regulatory T cells (Treg), Ara h 2-specific B cells and PN-specific sIgE and sIgG4 antibody levels.

In PN-allergic donors, PN sIgE levels increased until d28 after OFC, but to a variable extent. This variability was associated with a differential increase of Ara h 2⁺ B cells at d7, based on which we identified strong and weak responders (SR and WR). SR exhibited a more pronounced increase of PN sIgE, stronger in vivo activation of T and B cells (HLA-DR⁺, Ki-67⁺, CD21^-), as well as prominent induction of the low-affinity IgE receptor CD23 in Ara h 2⁺ B cells. In contrast, WR exhibited strong activation of PN-specific Tregs at d7. At baseline, SR and WR differed regarding Ara h 2⁺ memory B cells and frequencies of Th2 and type 2-driving Helios-expressing PN-specific Tconv. Minor changes in Th1 cells were also observed in non-allergic donors.

Our results indicate differential adaptive immune responses towards OFC in PN-allergic adults. In summary, SR displayed a more allergy-maintaining immune response, while WR displayed a rather suppressive immune response. Underlying responsible factors such as genetics, as well as clinical consequences, will require further investigation in larger cohorts.