Differences in IgG autoantibody Fab glycosylation across autoimmune diseases
Differences in IgG autoantibody Fab glycosylation across autoimmune diseases
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DOI：
10.1016/j.jaci.2022.10.035
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发表时间：
2023-06-05
影响因子：
14.2
通讯作者：
Rispens, Theo
中科院分区：
文献类型：
--
作者：
Koers, Jana;Sciarrillo, Rocco;Rispens, Theo
背景：已证实自身抗体Fab糖基化在几种自身免疫性疾病中普遍存在。目的:为了研究Fab糖基化升高是否是自身免疫的共同特征，本研究调查了与一系列不同B细胞介导的自身免疫性疾病相关的自身抗体血清IgG及其亚类的Fab糖基化水平，这些疾病包括类风湿关节炎、重症肌无力亚型、寻常型天疱疮、抗中性粒细胞细胞质抗体相关的血管炎、系统性红斑狼疮、抗肾小球基底膜肾小球肾炎、血栓性血小板减少性紫癜和格林-巴氏综合征。方法：采用凝集素亲和层析法和自身抗原特异性免疫法检测Fab糖基化IgG抗体水平。结果：在10例自身抗体应答中的6例中，在8种疾病中的5例中，研究者发现IgG自身抗体Fab糖基化水平升高，从类风湿性关节炎的86%到系统性红斑狼疮的26%不等。升高的自身抗体Fab糖基化并不局限于IgG4（已知易发生Fab糖基化），但也存在于IgG1中。当将慢性自身免疫性疾病与急性自身免疫性疾病进行比较时，Fab糖基化升高仅限于慢性疾病。作为慢性自身抗原暴露的代表，研究人员测定了针对常见潜伏疱疹病毒抗体的Fab糖基化水平，以及慢性hiv -1感染个体中糖蛋白120的水平。对这些病毒抗原的免疫与Fab糖基化水平升高无关，这表明慢性抗原刺激本身不会导致Fab糖基化水平升高。结论：这些数据表明，在慢性而非急性B细胞介导的自身免疫性疾病中，Fab聚糖富集了疾病特异性自身抗体。[J] .中华过敏症杂志，2002,21(1):16 - 16。
Background: Increased prevalence of autoantibody Fab glycosylation has been demonstrated for several autoimmune diseases. Objectives: To study whether elevated Fab glycosylation is a common feature of autoimmunity, this study investigated Fab glycosylation levels on serum IgG and its subclasses for autoantibodies associated with a range of different B cell- mediated autoimmune diseases, including rheumatoid arthritis, myasthenia gravis subtypes, pemphigus vulgaris, antineutrophil cytoplasmic antibody-associated vasculitis, systemic lupus erythematosus, anti-glomerular basement membrane glomerulonephritis, thrombotic thrombocytopenic purpura, and Guillain-Barre ⠁ syndrome. Methods: The level of Fab glycosylated IgG antibodies was assessed by lectin affinity chromatography and autoantigen-specific immunoassays. Results: In 6 of 10 autoantibody responses, in 5 of 8 diseases, the investigators found increased levels of Fab glycosylation on IgG autoantibodies that varied from 86% in rheumatoid arthritis to 26% in systemic lupus erythematosus. Elevated autoantibody Fab glycosylation was not restricted to IgG4, which is known to be prone to Fab glycosylation, but was also present in IgG1. When autoimmune diseases with a chronic disease course were compared with more acute autoimmune illnesses, increased Fab glycosylation was restricted to the chronic diseases. As a proxy for chronic autoantigen exposure, the investigators determined Fab glycosylation levels on antibodies to common latent herpes viruses, as well as to glycoprotein 120 in individuals who are chronically HIV-1-infected. Immunity to these viral antigens was not associated with increased Fab glycosylation levels, indicating that chronic antigen-stimulation as such does not lead to increased Fab glycosylation levels. Conclusions: These data indicate that in chronic but not acute B cell-mediated autoimmune diseases, disease-specific autoantibodies are enriched for Fab glycans. (J Allergy Clin Immunol 2023;151:16 46-54.)