Bang Holger, Egerer Karl, Gauliard Anke, Lüthke Kirsten, Rudolph Paul E, Fredenhagen Gert, Berg Wigbert, Feist Eugen, Burmester Gerd-R
Orgentec Diagnostika, Mainz, Germany.
Arthritis Rheum. 2007 Aug;56(8):2503-11. doi: 10.1002/art.22817.
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.
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.
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).
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.
抗原修饰是自身抗体产生的一个触发因素。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，而针对瓜氨酸化抗原的抗体检测已成为一个诊断里程碑。我们开展本研究以确定抗突变和瓜氨酸化波形蛋白（MCV）抗体是否可作为RA的诊断和预后标志物。
我们在RA患者的滑液中鉴定出人类MCV的新型异构体。通过分析自身抗体反应性来研究这些与疾病相关修饰的意义。在一组1151例RA患者中，将抗MCV酶联免疫吸附测定（ELISA）的诊断意义和预后价值与抗环瓜氨酸肽（抗CCP）ELISA进行比较。
在RA中，抗MCV和抗CCP检测的敏感性分别计算为82%和72%。两种检测的特异性相当（分别为98%和96%）。在对16例中度疾病活动的RA患者（28个关节的平均疾病活动评分[DAS28]为2.72）和26例活动期RA患者（平均DAS28为5.07）的随访分析中，使用抗MCV检测可以对RA进行疾病分层（P = 0.0084）。在42例RA患者中（在不同时间点进行了n = 427次抗体检测），记录到抗MCV抗体与DAS28有显著相关性（r = 0.5334，P = 0.0003）。
波形蛋白的抗原特性由突变和瓜氨酸化决定。抗MCV抗体是RA的一种新型诊断标志物。此外，它们可能有助于疾病监测，并且——如果在更多患者系列中得到证实——有助于疾病分层。
