TY - JOUR
T1 - Glycomic analysis of antibody indicates distinctive glycosylation profile in patients with autoimmune cholangitis
AU - Zhou, Xing
AU - Kailemia, Muchena J.
AU - Sun, Ying
AU - Shuai, Zongwen
AU - Yang, Guo Xiang
AU - Dhaliwal, Sandeep
AU - Cristoferi, Laura
AU - Leung, Patrick S.C.
AU - Invernizzi, Pietro
AU - Bowlus, Christopher
AU - Lebrilla, Carlito B.
AU - Ansari, Aftab A.
AU - Ridgway, William M.
AU - Zhang, Weici
AU - Gershwin, M. Eric
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
KW - Antibody
KW - Glycosylation
KW - Inflammation
KW - Primary biliary cholangitis
KW - Primary sclerosing cholangitis
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U2 - 10.1016/j.jaut.2020.102503
DO - 10.1016/j.jaut.2020.102503
M3 - Article
C2 - 32546343
AN - SCOPUS:85086568321
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
SN - 0896-8411
M1 - 102503
ER -