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Prevalence, persistence, and genetics of antibody responses to protein toxins and virulence factors
bioRxiv - Immunology Pub Date : 2021-10-02 , DOI: 10.1101/2021.10.01.462481
Julia W. Angkeow , Daniel R. Monaco , Athena Chen , Thiagarajan Venkataraman , Sahana Jayaraman , Cristian Valencia , Brandon M. Sie , Thomas Liechti , Payam Noroozi Farhadi , Gabriela Funez-dePagnier , Cheryl A. Sherman-Baust , May Q. Wong , Cynthia L. Sears , Patricia J. Simner , June L. Round , Priya Duggal , Uri Laserson , Theodore S. Steiner , Ranjan Sen , Thomas E. Lloyd , Mario Roederer , Andrew L. Mammen , Randy S. Longman , Lisa G. Rider , H. Benjamin Larman

Microbial exposures are crucial environmental factors that impact healthspan by sculpting the immune system and microbiota. Antibody profiling via programmable Phage ImmunoPrecipitation Sequencing (PhIP-Seq) provides a high-throughput, costeffective approach for multiplexed detection of exposure and response to thousands of microbial protein products. Here we designed and constructed a library of 95,601 56 amino acid peptide tiles spanning a subset of environmental proteins more likely to be associated with immune responses: those with “toxin” or “virulence factor” keyword annotations. PhIP-Seq was used to profile the circulating antibodies of ~1,000 individuals against this “ToxScan” library of 14,430 toxins and virulence factors from 1,312 genera of organisms. In addition to a detailed analysis of six commonly encountered human commensals and pathogens, we study the age-dependent stability of the ToxScan profile and use a genome-wide association study (GWAS) to find that the MHC-II locus modulates the selection of bacterial epitopes. We detect previously described anti-flagellin antibody responses in a Crohn’s disease cohort and identify a novel association between anti-flagellin antibodies and juvenile dermatomyositis (JDM). PhIP-Seq with the ToxScan library provides a new window into exposure and immune responses to environmental protein toxins and virulence factors, which can be used to study human health and disease at cohort scale.

中文翻译:

对蛋白质毒素和毒力因子的抗体反应的流行性、持续性和遗传学

微生物暴露是通过塑造免疫系统和微生物群来影响健康的关键环境因素。通过可编程噬菌体免疫沉淀测序 (PhIP-Seq) 进行的抗体分析提供了一种高通量、经济高效的方法,用于对数千种微生物蛋白质产品的暴露和反应进行多重检测。在这里,我们设计并构建了一个包含 95,601 个 56 氨基酸肽块的库,涵盖了更可能与免疫反应相关的环境蛋白质子集:那些带有“毒素”或“毒力因子”关键字注释的环境蛋白质。PhIP-Seq 用于分析大约 1,000 个人针对这个“ToxScan”文库的循环抗体,该文库包含来自 1,312 个生物属的 14,430 种毒素和毒力因子。除了对六种常见的人类共生菌和病原体进行详细分析外,我们还研究了 ToxScan 谱的年龄依赖性稳定性,并使用全基因组关联研究 (GWAS) 发现 MHC-II 基因座调节细菌的选择表位。我们检测了先前描述的克罗恩病队列中的抗鞭毛蛋白抗体反应,并确定了抗鞭毛蛋白抗体与幼年型皮肌炎 (JDM) 之间的新关联。带有 ToxScan 库的 PhIP-Seq 为了解环境蛋白质毒素和毒力因子的暴露和免疫反应提供了一个新窗口,可用于在队列规模研究人类健康和疾病。我们研究了 ToxScan 谱的年龄依赖性稳定性,并使用全基因组关联研究 (GWAS) 发现 MHC-II 基因座调节细菌表位的选择。我们检测了先前描述的克罗恩病队列中的抗鞭毛蛋白抗体反应,并确定了抗鞭毛蛋白抗体与幼年型皮肌炎 (JDM) 之间的新关联。带有 ToxScan 库的 PhIP-Seq 为了解环境蛋白质毒素和毒力因子的暴露和免疫反应提供了一个新窗口,可用于在队列规模研究人类健康和疾病。我们研究了 ToxScan 谱的年龄依赖性稳定性,并使用全基因组关联研究 (GWAS) 发现 MHC-II 基因座调节细菌表位的选择。我们检测了先前描述的克罗恩病队列中的抗鞭毛蛋白抗体反应,并确定了抗鞭毛蛋白抗体与幼年型皮肌炎 (JDM) 之间的新关联。带有 ToxScan 库的 PhIP-Seq 为了解环境蛋白质毒素和毒力因子的暴露和免疫反应提供了一个新窗口,可用于在队列规模研究人类健康和疾病。
更新日期:2021-10-06
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