Glycan biomarkers of autoimmunity and bile acid-associated alterations of the human glycome: Primary biliary cirrhosis and primary sclerosing cholangitis-specific glycans

Emanual Maverakis, Alexander A. Merleev, Dayoung Park, Muchena J. Kailemia, Gege Xu, L. Renee Ruhaak, Kyoungmi Kim, Qiuting Hong, Qiongyu Li, Patrick Leung, William Liakos, Yu Jui Yvonne Wan, Christopher L. Bowlus, Alina I. Marusina, Nelvish N. Lal, Yixuan Xie, Guillaume Luxardi, Carlito B. Lebrilla

Research output: Contribution to journalArticlepeer-review

Abstract

We have recently introduced multiple reaction monitoring (MRM) mass spectrometry as a novel tool for glycan biomarker research and discovery. Herein, we employ this technique to characterize the site-specific glycan alterations associated with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Glycopeptides associated with disease severity were also identified. Multinomial regression modelling was employed to construct and validate multi-analyte diagnostic models capable of accurately distinguishing PBC, PSC, and healthy controls from one another (AUC = 0.93 ± 0.03). Finally, to investigate how disease-relevant environmental factors can influence glycosylation, we characterized the ability of bile acids known to be differentially expressed in PBC to alter glycosylation. We hypothesize that this could be a mechanism by which altered self-antigens are generated and become targets for immune attack. This work demonstrates the utility of the MRM method to identify diagnostic site-specific glycan classifiers capable of distinguishing even related autoimmune diseases from one another.

Original languageEnglish (US)
Article number108825
JournalClinical Immunology
Volume230
DOIs
StatePublished - Sep 2021

Keywords

  • biomarker testing
  • Multiple Reaction Monitoring
  • N-glycopeptides
  • plasma
  • Primary Biliary Cirrhosis (PBC)
  • Primary Sclerosing Cholangitis (PSC)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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