Familian A, Voskuyl A E, van Mierlo G J, Heijst H A, Twisk J W R, Dijkmans B A C, Hack C E
Department of Immunopathology, Sanquin Research at the CLB, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands.
Ann Rheum Dis. 2005 Jul;64(7):1003-8. doi: 10.1136/ard.2004.029124.
Tumour necrosis factor (TNF) blocking agents decrease C reactive protein (CRP) levels in rheumatoid arthritis (RA). It has been shown that CRP may contribute to complement activation in RA.
To assess the effect of intravenous infliximab treatment on complement activation, especially that mediated by CRP, in RA.
35 patients with active RA (28 joint count Disease Activity Score (DAS28) >4.4) were treated with intravenous injections of infliximab (3 mg/kg, at weeks 0, 2, 6, 14, and 22). Clinical response and plasma levels of complement activation products, of CRP and of CRP-complement complexes, which are specific markers for CRP mediated complement activation, were assessed at the indicated time points up to 22 weeks. The relationship between CRP and CRP-complement complexes was analysed by paired t test between two time points and by generalised estimated equation, to test differences of variables over time.
At 2 weeks after the first dose, infliximab significantly reduced overall C3 and C4 activation and plasma levels of CRP and CRP-complement complexes were also significantly reduced at this time point. The effects of infliximab on CRP and complement continued throughout the observation period and were more pronounced in patients with a good response to infliximab treatment.
Treatment with infliximab decreases plasma levels of CRP and CRP dependent complement activation products and concomitantly may reduce complement activation in RA. Complement activation may be among the effector mechanisms of TNF in RA.
肿瘤坏死因子（TNF）阻断剂可降低类风湿关节炎（RA）患者的C反应蛋白（CRP）水平。已有研究表明，CRP可能在RA中促进补体激活。
评估静脉注射英夫利昔单抗治疗对RA患者补体激活的影响，尤其是由CRP介导的补体激活。
35例活动期RA患者（28个关节计数疾病活动评分（DAS28）>4.4）接受静脉注射英夫利昔单抗治疗（3mg/kg，分别在第0、2、6、14和22周）。在长达22周的指定时间点评估临床反应以及补体激活产物、CRP和CRP-补体复合物的血浆水平，CRP-补体复合物是CRP介导补体激活的特异性标志物。通过两个时间点之间的配对t检验和广义估计方程分析CRP与CRP-补体复合物之间的关系，以检验变量随时间的差异。
首次给药后2周，英夫利昔单抗显著降低了总体C3和C4激活，此时CRP和CRP-补体复合物的血浆水平也显著降低。英夫利昔单抗对CRP和补体的影响在整个观察期持续存在，且在对英夫利昔单抗治疗反应良好的患者中更为明显。
英夫利昔单抗治疗可降低CRP和CRP依赖性补体激活产物的血浆水平，并可能同时减少RA中的补体激活。补体激活可能是TNF在RA中的效应机制之一。
