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

Angkeow, J. W.; Monaco, D. R.; Chen, A.; Venkataraman, T.; Jayaraman, S.; Valencia, C.; Sie, B. M.; Liechti, T.; Farhadi, P. N.; Funez-dePagnier, G.; Sherman-Baust, C. A.; Wong, M. Q.; Sears, C. L.; Simner, P. J.; Round, J. L.; Duggal, P.; Laserson, U.; Steiner, T. S.; Sen, R.; Lloyd, T. E.; Roederer, M.; Mammen, A. L.; Longman, R. S.; Rider, L. G.; Larman, H. B.

doi:10.1101/2021.10.01.462481

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bioRxiv · 10.1101/2021.10.01.462481

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

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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 Crohns 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.

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Angkeow, J. W., Monaco, D. R., Chen, A., Venkataraman, T., Jayaraman, S., Valencia, C., Sie, B. M., Liechti, T., Farhadi, P. N., Funez-dePagnier, G., Sherman-Baust, C. A., Wong, M. Q., Sears, C. L., Simner, P. J., Round, J. L., Duggal, P., Laserson, U., Steiner, T. S., Sen, R., Lloyd, T. E., Roederer, M., Mammen, A. L., Longman, R. S., Rider, L. G., Larman, H. B.. 2021-10-02. Prevalence, persistence, and genetics of antibody responses to protein toxins and virulence factors. https://doi.org/10.1101/2021.10.01.462481

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