Bruns Alexandra, Nicaise-Roland Pascale, Hayem Gilles, Palazzo Elisabeth, Dieudé Philippe, Grootenboer-Mignot Sabine, Chollet-Martin Sylvie, Meyer Olivier
Rheumatology Department, Bichat Teaching Hospital, AP-HP, CHU Bichat, 46 rue Henri Huchard, 75018 Paris, France.
Joint Bone Spine. 2009 May;76(3):248-53. doi: 10.1016/j.jbspin.2008.09.010. Epub 2009 Feb 8.
Antibodies to cyclic citrullinated peptide (anti-CCP) and IgM rheumatoid factor (IgM-RF) are well-established serological markers for rheumatoid arthritis (RA). Lupus-like disease with antinuclear antibodies (ANA) has been reported during TNFalpha antagonist therapy. Our objectives were to investigate the effect of infliximab therapy on these three autoantibodies in patients with established RA and to look for correlations linking IgM-RF and anti-CCP titres to a treatment response (defined as a good or moderate EULAR response) after 48 weeks of infliximab therapy.
Thirty-six patients with long-standing RA not responding to disease-modifying anti-rheumatic drugs (DMARDs) received intravenous infliximab (starting dose: 3mg/kg) at 0, 2, and 6 weeks then at 8-week intervals, in combination with a DMARD. At baseline, week 24, and week 48, C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were determined and the disease activity score (DAS28) was calculated. Serum samples collected at the same time points were used to measure anti-CCP (commercial second-generation ELISA), IgM-RF (quantitative nephelometric assay), and ANA (indirect immunofluorescence in HEp2 cells). Correlations linking baseline autoantibody titres to changes in autoantibody levels were examined.
At baseline, tests were positive for anti-CCP in 31/36 (94.6%) patients, IgM-RF in 29/36 (80.5%) patients, and ANA in 16/36 (44%) patients. IgM-RF titres decreased significantly (p<0.001), whereas anti-CCP showed little change (p=0.053). ANA titres increased significantly (p<0.001). The treatment response was not associated with changes in anti-CCP or IgM-RF titres during infliximab therapy (OR for a response in patients with a 50% anti-CCP decrease, 0.77 [95%CI, 0.16-3.58]; OR for a response in patients with a 50% IgM-RF decrease, 0.82 [95%CI, 0.16-4.13]).
During infliximab therapy used to treat established RA, IgM-RF titres showed larger decreases than anti-CCP titres. Changes in IgM-RF and anti-CCP failed to correlate with the 48-week treatment response.
抗环瓜氨酸肽抗体（抗CCP）和IgM类风湿因子（IgM-RF）是类风湿关节炎（RA）公认的血清学标志物。有报道称，在使用肿瘤坏死因子α拮抗剂治疗期间会出现伴有抗核抗体（ANA）的狼疮样疾病。我们的目的是研究英夫利昔单抗治疗对确诊RA患者这三种自身抗体的影响，并寻找在英夫利昔单抗治疗48周后将IgM-RF和抗CCP滴度与治疗反应（定义为良好或中度欧洲抗风湿病联盟反应）联系起来的相关性。
36例对改善病情抗风湿药物（DMARDs）无反应的长期RA患者在第0、2和6周接受静脉注射英夫利昔单抗（起始剂量：3mg/kg），然后每8周一次，并联合使用一种DMARD。在基线、第24周和第48周，测定C反应蛋白（CRP）和红细胞沉降率（ESR），并计算疾病活动评分（DAS28）。在相同时间点采集的血清样本用于检测抗CCP（商用第二代ELISA）、IgM-RF（定量散射比浊法）和ANA（HEp2细胞间接免疫荧光法）。检查将基线自身抗体滴度与自身抗体水平变化联系起来的相关性。
在基线时，31/36（94.6%）的患者抗CCP检测呈阳性，29/36（80.5%）的患者IgM-RF检测呈阳性，16/36（44%）的患者ANA检测呈阳性。IgM-RF滴度显著下降（p<0.001），而抗CCP变化不大（p=0.053）。ANA滴度显著升高（p<0.001）。治疗反应与英夫利昔单抗治疗期间抗CCP或IgM-RF滴度的变化无关（抗CCP下降50%的患者反应的OR为0.77[95%CI，0.16-3.58]；IgM-RF下降50%的患者反应的OR为0.82[95%CI，0.16-4.13]）。
在用于治疗确诊RA的英夫利昔单抗治疗期间，IgM-RF滴度的下降幅度大于抗CCP滴度。IgM-RF和抗CCP的变化与48周治疗反应无关。
