Glycomic analysis of antibody indicates distinctive glycosylation profile in patients with autoimmune cholangitis

Xing Zhou, Muchena J. Kailemia, Ying Sun, Zongwen Shuai, Guo Xiang Yang, Sandeep Dhaliwal, Laura Cristoferi, Patrick S.C. Leung, Pietro Invernizzi, Christopher Bowlus, Carlito B. Lebrilla, Aftab A. Ansari, William M. Ridgway, Weici Zhang, M. Eric Gershwin

Research output: Contribution to journalArticle

Abstract

Glycosylation of antibodies, particularly in the Fc domain, critically modulate the ability of antibodies to bind to FcRs, maintaining immune quiescence to achieve a finely orchestrated immune response. The removal of sialic acid and galactose residues dramatically alters the physiological function of IgGs, and alterations of Ig glycosylation have been associated with several autoimmune disorders. However, Ig glycosylation has not been extensively studied in autoimmune cholangitis. We applied triple quadruple mass spectroscopy with subsequent multiple reaction monitoring to elucidate the profile, composition and linkage of sugar residues of antibody glycans in patients with primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and healthy controls (HC). Agalactosylated, HexNAc terminated IgG1 glycoforms were enriched in both PBC and PSC. Levels of IgM glycans at site N439 and fucosylated glycans in J chain, were significantly decreased in PBC compared to PSC and HC. PSC patients had decreased bisecting glycoforms and increased biantennary glycoforms on IgA compared to PBC. Importantly, our data demonstrate the association of distinct branching and composition patterns of Ig glycoforms with disease severity and liver cirrhosis, which highlight the importance of glycan biology as a potential mechanism and/or a disease specific signal of inflammation.

Original languageEnglish (US)
Article number102503
JournalJournal of autoimmunity
DOIs
StateAccepted/In press - Jan 1 2020

Keywords

  • Antibody
  • Glycosylation
  • Inflammation
  • Primary biliary cholangitis
  • Primary sclerosing cholangitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Zhou, X., Kailemia, M. J., Sun, Y., Shuai, Z., Yang, G. X., Dhaliwal, S., Cristoferi, L., Leung, P. S. C., Invernizzi, P., Bowlus, C., Lebrilla, C. B., Ansari, A. A., Ridgway, W. M., Zhang, W., & Gershwin, M. E. (Accepted/In press). Glycomic analysis of antibody indicates distinctive glycosylation profile in patients with autoimmune cholangitis. Journal of autoimmunity, [102503]. https://doi.org/10.1016/j.jaut.2020.102503