Integrative transcriptomic analysis reveals key drivers of acute peanut allergic reactions.

Publication Type
Journal Article
Year of Publication
Watson, C T; Cohain, A T; Griffin, R S; Chun, Y; Grishin, A; Hacyznska, H; Hoffman, G E; Beckmann, N D; Shah, H; Dawson, P; Henning, A; Wood, R; Burks, A W; Jones, S M; Leung, D Y M; Sicherer, S; Sampson, H A; Sharp, A J; Schadt, E E; Bunyavanich, S
Nat Commun
Date Published
2017 12 05
Acute-Phase Reaction; Adolescent; CD4-Positive T-Lymphocytes; Child; Double-Blind Method; Enoyl-CoA Hydratase; Female; Gene Expression Profiling; Gene Regulatory Networks; Humans; Inflammation; Macrophages; Male; Microfilament Proteins; Nerve Tissue Proteins; Neutrophils; Peanut Hypersensitivity; Protein Phosphatase 1; Protein-Arginine Deiminase Type 4; Protein-Arginine Deiminases; Random Allocation; Receptors, Interleukin-1 Type II; Receptors, Leukotriene B4; Reproducibility of Results; RNA, Messenger

Mechanisms driving acute food allergic reactions have not been fully characterized. We profile the dynamic transcriptome of acute peanut allergic reactions using serial peripheral blood samples obtained from 19 children before, during, and after randomized, double-blind, placebo-controlled oral challenges to peanut. We identify genes with changes in expression triggered by peanut, but not placebo, during acute peanut allergic reactions. Network analysis reveals that these genes comprise coexpression networks for acute-phase response and pro-inflammatory processes. Key driver analysis identifies six genes (LTB4R, PADI4, IL1R2, PPP1R3D, KLHL2, and ECHDC3) predicted to causally modulate the state of coregulated networks in response to peanut. Leukocyte deconvolution analysis identifies changes in neutrophil, naive CD4 T cell, and macrophage populations during peanut challenge. Analyses in 21 additional peanut allergic subjects replicate major findings. These results highlight key genes, biological processes, and cell types that can be targeted for mechanistic study and therapeutic targeting of peanut allergy.