Remission of peanut allergy is associated with rewiring of allergen-driven T helper 2-related gene networks.

Abstract

The immunological changes underpinning acquisition of remission (also called sustained unresponsiveness) following food immunotherapy remain poorly defined. Limited access to effective therapies and biosamples from treatment responders has prevented progress. Probiotic peanut oral immunotherapy is highly effective at inducing remission, providing an opportunity to investigate immune changes. Using a systems biology approach, we examined gene co-expression network patterns in peanut-specific CD4+ T cell responses before and after probiotic and peanut oral immunotherapy in subjects enrolled in the PPOIT-001 randomized trial: Responders who attained remission (n=16), placebo-treated who remained allergic (n=16). Acquisition of remission was associated with rewiring of gene network patterns, which was characterized by integration of T helper 2 and interferon signalling modules, markedly reduced T helper 2gene connectivity, and shutdown in co-expression activity between T helper 2 effectors and cell cycle regulators. The immunological changes underlying remission following peanut oral immunotherapy are mediated by reprogramming of T helper 2-associated gene networks in the CD4+ T cell compartment. Findings provide insight into immune mechanisms driving the acquisition of remission following oral immunotherapy, paving the way for the development of improved approaches to induce remission/sustained unresponsiveness in patients with food allergy.