Immunoglobulin 1 (IgG1) Fc-glycosylation profiling of anti-citrullinated peptide antibodies from human serum
Immunoglobulin 1 (IgG1) Fc-glycosylation profiling of anti-citrullinated peptide antibodies from human serum
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DOI：
10.1002/prca.200800098
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发表时间：
2009-01-01
影响因子：
2
通讯作者：
Wuhrer, Manfred
中科院分区：
文献类型：
--
作者：
Scherer, H. Ulrich;Wang, Jun;Wuhrer, Manfred
在包括类风湿性关节炎（RA）在内的几种自身免疫性疾病中，自身抗体被认为是致病性的驱动力。已知人Ig的Fc部分的糖基化调节生物活性。然而，主要在总血清IgG水平上分析了人IgG-Fc的糖基化，揭示了RA中的半乳糖基化降低。鉴于PA中自身抗体的致病相关性，我们希望在本研究中解决在抗原特异性IgG亚群水平上是否可观察到不同的Fc-糖基化特征的问题。为此目的，我们已经开发了一种用于抗瓜氨酸肽抗体（ACPA）的微量纯化和Fc-糖基化分析的方法。ACPA代表一组在RA患者中以独特特异性出现的自身抗体。它们的存在与炎性疾病活动增加和快速关节破坏有关。结果表明，ACPA的IgG I亚类有很大的不同，从总血清IgG I方面的Fc-半乳糖基化，与半乳糖基化ACPA高于血清IgG 1的一些患者，而其他患者表现出较高的半乳糖基化血清IgG 1比ACPA。使用这种方法，可以对R-A患者队列中ACPA糖基化的生物学和临床相关性进行研究。
In several autoimmune disorders, including rheumatoid arthritis (RA), autoantibodies are thought to be the driving force of pathogenicity. Glycosylation of the Fc-part of human Igs is known to modulate biological activity. Hitherto, glycosylation of human IgG-Fc has been analyzed predominantly at the level of total serum IgG, revealing reduced galactosylation in RA. Given the pathogenic relevance of autoantibodies in PA, we wished, in the present study, to address the question whether distinct Fc-glycosylation features are observable at the level of antigen-specific IgG subpopulations. For this purpose, we have developed a method for the microscale purification and Fc-glycosylation analysis of anti-citrullinated peptide antibodies (ACPA). ACPA represent a group of autoantibodies that occur with unique specificity in RA patients. Their presence is associated with increased inflammatory disease activity and rapid joint destruction. Results indicate that ACPA of the IgG I subclass vary considerably from total serum IgG I with respect to Fc-galactosylation, with galactosylation being higher on ACPA than on serum IgG1 for some patients, while other patients show higher galactosylation on serum IgG1 than on ACPA. Using this method, studies can be performed on the biological and clinical relevance of ACPA glycosylation within R-A patient cohorts.