@article{e33e6bffa5a7482f944135a082163776,
title = "Integrative transcriptomic analysis reveals key drivers of acute peanut allergic reactions",
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.",
author = "Watson, {C. T.} and Cohain, {A. T.} and Griffin, {R. S.} and Y. Chun and A. Grishin and H. Hacyznska and Hoffman, {G. E.} and Beckmann, {N. D.} and H. Shah and P. Dawson and A. Henning and R. Wood and Burks, {A. W.} and Jones, {S. M.} and Leung, {D. Y.M.} and S. Sicherer and Sampson, {H. A.} and Sharp, {A. J.} and Schadt, {E. E.} and S. Bunyavanich",
note = "Funding Information: We thank the participating subjects and their families who made this study possible. We thank Dr. Marshall Plaut, CoFAR scientific and medical officer and chief of the National Institute of Allergy and Infectious Diseases, Food Allergy, Atopic Dermatitis, and Allergic Mechanisms Section. We thank the staff of the clinical research units at each institution and the Statistical and Clinical Coordinating Center. We also thank the Mount Sinai Genomics Core and Scientific Computing at the Icahn School of Medicine at Mount Sinai. This study was supported by the National Institutes of Health (K08AI093538, R01AI118833, U19AI066738, and U01AI066560) and the Mindich Child Health and Development Institute at Mount Sinai. The project was also supported by grant nos. UL1 TR-000154 (National Jewish), UL1 TR-000067 (Mount Sinai), UL1 TR-000039 (Arkansas), UL1 TR-000083 (U North Carolina) and UL1 TR-000424 (Johns Hopkins) from the National Center for Research Resources (NCRR), a component of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2017 The Author(s).",
year = "2017",
month = dec,
day = "1",
doi = "10.1038/s41467-017-02188-7",
language = "English",
volume = "8",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}