Evaluation of classical complement pathway activation in rheumatoid arthritis - Measurement of C1q-C4 complexes as novel activation products
Evaluation of classical complement pathway activation in rheumatoid arthritis - Measurement of C1q-C4 complexes as novel activation products
复制标题
DOI：
10.1002/art.21729
复制
发表时间：
2006-04-01
影响因子：
--
通讯作者：
Hack, CE
中科院分区：
文献类型：
--
作者：
Wouters, D;Voskuyl, AE;Hack, CE
Objective.最近在经典补体途径中描述了稳定且对体外伪影敏感性最低的新型活化产物。本研究评估了这些产品的循环水平，即，类风湿性关节炎（RA）患者血浆样本中经典途径（C1 q）识别分子和活化C4之间的共价复合物，以建立这些水平与这些患者的临床和免疫学参数之间的关系。测定了41例活动性RA患者和43例非活动性RA患者的血浆样本中C1 q-C4水平。根据28个关节疾病活动性评分（DAS 28），使用斯皮尔曼等级相关性，这些水平与其他补体激活产物和疾病活动性相关。活动性RA患者的C1 q-C4血浆水平显著高于临床缓解期RA患者（中位数3.3个任意单位[Au]，范围0.4-13.4 vs 1.7个Au，范围0.2-5.5; P = 0.0001），表明经典补体途径的激活反映了疾病活动性。C1 q-C4水平与DAS 28之间的显著相关性支持了这一点（r = 0.398，P = 0.0002）。与非活动性疾病患者相比，活动性疾病患者的其他补体活化产物（如活化C4（C4 b/c））水平也显著升高（P = 0.03），并与C1 q-C4水平相关（r = 0.329，P = 0.002）。C1 q-C4复合物水平在滑液样本中高于血浆样本。RA患者通过经典途径的全身补体激活与疾病活动相关。这些结果表明，C1 q-C4复合物可用作RA的生物标志物。
Objective. Novel activation products that are stable and minimally susceptible to in vitro artefacts have recently been described in the classical complement pathway. The present study assessed circulating levels of these products, i.e., covalent complexes between the recognition molecule of the classical pathway (C1q) and activated C4, in plasma samples from patients with rheumatoid arthritis (RA) to establish the relationship between these levels and the clinical and immunologic parameters in these patients.Methods. C1q-C4 levels were measured in plasma samples from 41 patients with active RA and 43 patients with inactive RA. These levels were related to other complement activation products and to disease activity according to the Disease Activity Score in 28 joints (DAS28), using Spearman's rank correlations.Results. C1q-C4 plasma levels were significantly higher in patients with active RA as compared with patients with RA in clinical remission (median 3.3 arbitrary units [AU], range 0.4-13.4 versus 1.7 AU, range 0.2-5.5; P = 0.0001), suggesting that activation of the classical complement pathway reflects disease activity. This was supported by a significant correlation between C1q-C4 levels and the DAS28 (r = 0.398, P = 0.0002). Levels of other complement activation products, such as activated C4 (C4b/c), were also significantly elevated in patients with active disease compared with patients with inactive disease (P = 0.03), and were correlated with C1q-C4 levels (r = 0.329, P = 0.002). Levels of C1q-C4 complexes were higher in synovial fluid samples than in plasma samples from the 4 patients tested.Conclusion. Systemic complement activation via the classical pathway in patients with RA correlates with disease activity. These results indicate that C1q-C4 complexes may be used as a biomarker for RA.