Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
Nat Commun. 2017 Dec 5;8(1):1943. doi: 10.1038/s41467-017-02188-7.
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.
导致急性食物过敏反应的机制尚未完全阐明。我们使用来自 19 名儿童的系列外周血样本，对花生进行随机、双盲、安慰剂对照口服挑战前后的急性花生过敏反应进行了动态转录组分析。我们鉴定了在急性花生过敏反应期间由花生而非安慰剂触发的表达变化的基因。网络分析显示，这些基因构成了急性反应和促炎过程的共表达网络。关键驱动因素分析确定了六个基因（LTB4R、PADI4、IL1R2、PPP1R3D、KLHL2 和 ECHDC3），这些基因被预测能够因果调节对花生的核心调控网络的状态。白细胞去卷积分析鉴定了在花生挑战期间中性粒细胞、幼稚 CD4 T 细胞和巨噬细胞群体的变化。在另外 21 名花生过敏患者中的分析复制了主要发现。这些结果突出了可以针对机制研究和花生过敏的治疗靶向的关键基因、生物过程和细胞类型。
