Integrative transcriptomic analysis reveals key drivers of acute peanut allergic reactions

C. T. Watson, A. T. Cohain, R. S. Griffin, Y. Chun, A. Grishin, H. Hacyznska, G. E. Hoffman, N. D. Beckmann, H. Shah, P. Dawson, A. Henning, R. Wood, A. W. Burks, S. M. Jones, D. Y. M. Leung, S. Sicherer, H. A. Sampson, A. J. Sharp, E. E. Schadt and S. Bunyavanich ()
Additional contact information
C. T. Watson: Icahn School of Medicine at Mount Sinai
A. T. Cohain: Icahn School of Medicine at Mount Sinai
R. S. Griffin: Hospital for Special Surgery
Y. Chun: Icahn School of Medicine at Mount Sinai
A. Grishin: Icahn School of Medicine at Mount Sinai
H. Hacyznska: Icahn School of Medicine at Mount Sinai
G. E. Hoffman: Icahn School of Medicine at Mount Sinai
N. D. Beckmann: Icahn School of Medicine at Mount Sinai
H. Shah: Icahn School of Medicine at Mount Sinai
P. Dawson: eEmmes Corporation
A. Henning: eEmmes Corporation
R. Wood: Johns Hopkins University
A. W. Burks: University of North Carolina
S. M. Jones: University of Arkansas for Medical Sciences and Arkansas Children’s Hospital
D. Y. M. Leung: National Jewish Health
S. Sicherer: Icahn School of Medicine at Mount Sinai
H. A. Sampson: Icahn School of Medicine at Mount Sinai
A. J. Sharp: Icahn School of Medicine at Mount Sinai
E. E. Schadt: Icahn School of Medicine at Mount Sinai
S. Bunyavanich: Icahn School of Medicine at Mount Sinai

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-02188-7

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