Prevalence, persistence, and genetics of antibody responses to protein toxins and virulence factors

作者：Julia W. Angkeow, Daniel R. Monaco, Athena Chen, Thiagarajan Venkataraman, Sahana Jayaraman, Cristian Valencia, Brandon 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 Longman, Lisa G. Rider, H. Benjamin Larman · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2021 · DOI：10.1101/2021.10.01.462481 · 被引用次数：4 · 研究领域：Inflammatory Myopathies and Dermatomyositis、T-cell and B-cell Immunology、Celiac Disease Research and Management

Abstract 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.