An efficient urine peptidomics workflow identifies chemically defined dietary gluten peptides from patients with celiac disease

Author:

Palanski Brad A.,Weng Nielson,Zhang LichaoORCID,Hilmer Andrew J.,Fall Lalla A.,Swaminathan KavyaORCID,Jabri Bana,Sousa CarolinaORCID,Fernandez-Becker Nielsen Q.,Khosla Chaitan,Elias Joshua E.ORCID

Abstract

AbstractCeliac disease (CeD) is an autoimmune disorder induced by consuming gluten proteins from wheat, barley, and rye. Glutens resist gastrointestinal proteolysis, resulting in peptides that elicit inflammation in patients with CeD. Despite well-established connections between glutens and CeD, chemically defined, bioavailable peptides produced from dietary proteins have never been identified from humans in an unbiased manner. This is largely attributable to technical challenges, impeding our knowledge of potentially diverse peptide species that encounter the immune system. Here, we develop a liquid chromatographic-mass spectrometric workflow for untargeted sequence analysis of the urinary peptidome. We detect over 600 distinct dietary peptides, of which ~35% have a CeD-relevant T cell epitope and ~5% are known to stimulate innate immune responses. Remarkably, gluten peptides from patients with CeD qualitatively and quantitatively differ from controls. Our results provide a new foundation for understanding gluten immunogenicity, improving CeD management, and characterizing the dietary and urinary peptidomes.

Funder

U.S. Department of Health & Human Services | National Institutes of Health

Ministerio de Ciencia e Innovación from Spain and FEDER funds

The Joint Institute for Metrology in Biology Seed Grant, founded by the National Institute of Standards and Technology

Chan Zuckerberg Biohub

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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