Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis
Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis
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DOI：
10.1002/art.22817
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发表时间：
2007-08-01
影响因子：
--
通讯作者：
Burmester, Gerd-R.
中科院分区：
文献类型：
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作者：
Bang, Holger;Egerer, Karl;Burmester, Gerd-R.
Objective.抗原的修饰代表了自身抗体产生的触发因素。在类风湿性关节炎（RA）的发病机制中，蛋白质的瓜氨酸化已被证明是一个关键过程，并且针对瓜氨酸化抗原的抗体的测定已成为诊断的里程碑。我们进行了这项研究，以确定是否突变和瓜氨酸波形蛋白（MCV）的抗体可以作为一个诊断和RA的预后标志物。我们在类风湿关节炎患者的滑液中发现了人类MCV的新亚型。通过自身抗体反应性分析研究了这些疾病相关修饰的意义。在一组1,151例RA患者中，将抗MCV酶联免疫吸附试验（ELISA）与抗环瓜氨酸肽（抗CCP）ELISA的诊断意义和预后价值进行比较。在RA中，抗MCV和抗CCP测定的敏感性分别为82%和72%。两种检测方法的特异性相当（分别为98%和96%）。在对16例中度疾病活动性RA患者（28个关节的平均疾病活动性评分[DAS 28]为2.72）和26例活动性疾病RA患者（平均DAS 28为5.07）进行的随访分析中，使用抗MCV试验可能对RA进行疾病分层（P = 0.0084）。在42例RA患者中（n = 427），抗MCV抗体与DAS 28呈显著相关（r = 0.5334，P = 0.0003）。波形蛋白的抗原特性通过突变和瓜氨酸来确定。抗MCV抗体是一种新的RA诊断标志物。此外，它们可以允许监测，如果在更大的患者系列中得到证实，还可以对疾病进行分层。
Objective. Modification of antigens represents a trigger for the generation of autoantibodies. In the pathogenesis of rheumatoid arthritis (RA), citrullination of proteins has been shown to be a critical process, and the determination of antibodies against citrullinated antigens has been a diagnostic milestone. We undertook this study to determine whether antibodies to mutated and citrullinated vimentin (MCV) could serve as a diagnostic and prognostic marker for RA.Methods. We identified novel isoforms of human MCV in the synovial fluid of RA patients. The significance of these disease-related modifications was investigated by the analysis of autoantibody reactivities. In a group of 1,151 RA patients, the diagnostic significance and the prognostic value of an anti-MCV enzyme-linked immunosorbent assay (ELISA) were compared with that of an anti-cyclic citrullinated peptide (anti-CCP) ELISA.Results. In RA, sensitivities of 82% and 72% were calculated for the anti-MCV and anti-CCP assays, respectively. The specificity of both assays was comparable (98% and 96%, respectively). In followup analyses of 16 RA patients with moderate disease activity (mean Disease Activity Score in 28 joints [DAS28] of 2.72) and 26 RA patients with active disease (mean DAS28 of 5.07), disease stratification of RA was possible using the anti-MCV assay (P = 0.0084). A significant correlation of anti-MCV antibodies with the DAS28 was documented (r = 0.5334, P = 0.0003), in 42 RA patients (n = 427 antibody determinations at different time points).Conclusion. Antigenic properties of vimentin were determined by mutation and citrullination. Anti-MCV antibodies are a novel diagnostic marker for RA. Furthermore, they may allow monitoring and-if confirmed in even larger series of patients-stratification of disease.