1. Glycan biomarkers of autoimmunity and bile acid-associated alterations of the human glycome: Primary biliary cirrhosis and primary sclerosing cholangitis-specific glycans.
- Author
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Maverakis E, Merleev AA, Park D, Kailemia MJ, Xu G, Ruhaak LR, Kim K, Hong Q, Li Q, Leung P, Liakos W, Wan YY, Bowlus CL, Marusina AI, Lal NN, Xie Y, Luxardi G, and Lebrilla CB
- Subjects
- B-Lymphocytes immunology, B-Lymphocytes metabolism, Bile Acids and Salts blood, Bile Acids and Salts immunology, Biomarkers blood, Case-Control Studies, Cholangitis, Sclerosing blood, Cholangitis, Sclerosing diagnosis, Diagnosis, Differential, Glycomics methods, Glycopeptides blood, Glycopeptides immunology, Glycosylation, Humans, Liver Cirrhosis, Biliary blood, Liver Cirrhosis, Biliary diagnosis, Polysaccharides blood, Spectrometry, Mass, Electrospray Ionization methods, Autoimmunity, Cholangitis, Sclerosing immunology, Liver Cirrhosis, Biliary immunology, Polysaccharides immunology
- 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., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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