Department of Immunopathology, Landsteiner Laboratory, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
J Allergy Clin Immunol. 2023 Jun;151(6):1646-1654. doi: 10.1016/j.jaci.2022.10.035. Epub 2023 Jan 27.
Increased prevalence of autoantibody Fab glycosylation has been demonstrated for several autoimmune diseases.
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-Barré syndrome.
The level of Fab glycosylated IgG antibodies was assessed by lectin affinity chromatography and autoantigen-specific immunoassays.
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 IgG, which is known to be prone to Fab glycosylation, but was also present in IgG. 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.
These data indicate that in chronic but not acute B cell-mediated autoimmune diseases, disease-specific autoantibodies are enriched for Fab glycans.
已经证明，几种自身免疫性疾病的自身抗体 Fab 糖基化程度增加。
为了研究 Fab 糖基化是否是自身免疫的一个共同特征，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的血清 IgG 及其亚类的 Fab 糖基化水平，包括类风湿关节炎、重症肌无力亚型、寻常型天疱疮、抗中性粒细胞胞质抗体相关性血管炎、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-巴利综合征。
通过凝集素亲和层析和自身抗原特异性免疫测定来评估 Fab 糖基化 IgG 抗体的水平。
在 10 种自身抗体反应中的 6 种、8 种疾病中的 5 种中，研究人员发现 IgG 自身抗体的 Fab 糖基化水平升高，范围从类风湿关节炎的 86%到系统性红斑狼疮的 26%。升高的自身抗体 Fab 糖基化不仅限于已知易于 Fab 糖基化的 IgG，而且也存在于 IgG 中。当将慢性病程的自身免疫性疾病与更急性的自身免疫性疾病进行比较时，Fab 糖基化增加仅限于慢性疾病。作为慢性自身抗原暴露的替代物，研究人员测定了慢性 HIV-1 感染个体对常见潜伏性疱疹病毒以及糖蛋白 120 的抗体的 Fab 糖基化水平。对这些病毒抗原的免疫反应与 Fab 糖基化水平的增加无关，表明单纯的慢性抗原刺激不会导致 Fab 糖基化水平的增加。
这些数据表明，在慢性但不是急性 B 细胞介导的自身免疫性疾病中，疾病特异性自身抗体富含 Fab 聚糖。
