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Glycomic analysis of antibody indicates distinctive glycosylation profile in patients with autoimmune cholangitis.
Journal of Autoimmunity ( IF 7.9 ) Pub Date : 2020-06-13 , DOI: 10.1016/j.jaut.2020.102503
Xing Zhou 1 , Muchena J Kailemia 2 , Ying Sun 3 , Zongwen Shuai 4 , Guo-Xiang Yang 5 , Sandeep Dhaliwal 6 , Laura Cristoferi 7 , Patrick S C Leung 5 , Pietro Invernizzi 7 , Christopher L Bowlus 6 , Carlito B Lebrilla 2 , Aftab A Ansari 5 , William M Ridgway 5 , Weici Zhang 5 , M Eric Gershwin 5
Affiliation  

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.



中文翻译:

抗体的糖组学分析表明自身免疫性胆管炎患者具有独特的糖基化特征。

抗体的糖基化,特别是在 Fc 域中,严重调节抗体与 FcR 结合的能力,维持免疫静止以实现精心策划的免疫反应。唾液酸和半乳糖残基的去除显着改变了 IgG 的生理功能,并且 Ig 糖基化的改变与几种自身免疫性疾病有关。然而,尚未在自身免疫性胆管炎中广泛研究 Ig 糖基化。我们应用三重四极杆质谱和随后的多反应监测来阐明原发性胆汁性胆管炎 (PBC)、原发性硬化性胆管炎 (PSC) 和健康对照 (HC) 患者中抗体聚糖的糖残基的分布、组成和联系。无乳糖,HexNAc 终止的 IgG1 糖型在 PBC 和 PSC 中均富集。与 PSC 和 HC 相比,PBC 中 N439 位点的 IgM 聚糖和 J 链岩藻糖基化聚糖的水平显着降低。与 PBC 相比,PSC 患者对 IgA 的二等分糖型减少,双触角糖型增加。重要的是,我们的数据证明了 Ig 糖型的不同分支和组成模式与疾病严重程度和肝硬化之间的关联,这突出了聚糖生物学作为潜在机制和/或炎症的疾病特异性信号的重要性。

更新日期:2020-08-20
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