Rheumatology Service, Hospital Clínic of Barcelona, IDIBAPS, Villarroel 170, 08036 Barcelona, Spain.
Arthritis Res Ther. 2009;11(5):R135. doi: 10.1186/ar2802. Epub 2009 Sep 2.
Evidence suggests that citrullinated fibrin(ogen) may be a potential in vivo target of anticitrullinated protein/peptide antibodies (ACPA) in rheumatoid arthritis (RA). We compared the diagnostic yield of three enzyme-linked immunosorbent assay (ELISA) tests by using chimeric fibrin/filaggrin citrullinated synthetic peptides (CFFCP1, CFFCP2, CFFCP3) with a commercial CCP2-based test in RA and analyzed their prognostic values in early RA.
Samples from 307 blood donors and patients with RA (322), psoriatic arthritis (133), systemic lupus erythematosus (119), and hepatitis C infection (84) were assayed by using CFFCP- and CCP2-based tests. Autoantibodies also were analyzed at baseline and during a 2-year follow-up in 98 early RA patients to determine their prognostic value.
With cutoffs giving 98% specificity for RA versus blood donors, the sensitivity was 72.1% for CFFCP1, 78.0% for CFFCP2, 71.4% for CFFCP3, and 73.9% for CCP2, with positive predictive values greater than 97% in all cases. CFFCP sensitivity in RA increased to 80.4% without losing specificity when positivity was considered as any positive anti-CFFCP status. Specificity of the three CFFCP tests versus other rheumatic populations was high (> 90%) and similar to those for the CCP2. In early RA, CFFCP1 best identified patients with a poor radiographic outcome. Radiographic progression was faster in the small subgroup of CCP2-negative and CFFCP1-positive patients than in those negative for both autoantibodies. CFFCP antibodies decreased after 1 year, but without any correlation with changes in disease activity.
CFFCP-based assays are highly sensitive and specific for RA. Early RA patients with anti-CFFCP1 antibodies, including CCP2-negative patients, show greater radiographic progression.
有证据表明,瓜氨酸化纤维蛋白(原)可能是类风湿关节炎(RA)中抗瓜氨酸蛋白/肽抗体(ACPA)的潜在体内靶标。我们比较了三种酶联免疫吸附试验(ELISA)检测方法的诊断效果,使用嵌合纤维蛋白/微丝蛋白瓜氨酸合成肽(CFFCP1、CFFCP2、CFFCP3)与基于 CCP2 的商业检测方法,并分析了它们在早期 RA 中的预后价值。
采用基于 CFFCP 和 CCP2 的检测方法对 307 名献血者和 RA 患者(322 例)、银屑病关节炎(133 例)、系统性红斑狼疮(119 例)和丙型肝炎感染(84 例)的样本进行了检测。还对 98 例早期 RA 患者进行了基线和 2 年随访的自身抗体分析,以确定其预后价值。
以 98%特异性区分 RA 与献血者的截断值为基础,CFFCP1 的敏感性为 72.1%,CFFCP2 为 78.0%,CFFCP3 为 71.4%,CCP2 为 73.9%,在所有情况下,阳性预测值均大于 97%。当将阳性结果视为任何阳性抗 CFFCP 状态时,CFFCP 在 RA 中的敏感性增加到 80.4%,而特异性不变。与其他风湿性疾病人群相比,三种 CFFCP 检测方法的特异性均较高(>90%),与 CCP2 相似。在早期 RA 中,CFFCP1 可最好地识别出影像学预后不良的患者。在 CCP2 阴性和 CFFCP1 阳性的小亚组患者中,影像学进展速度快于两种自身抗体均阴性的患者。CFFCP 抗体在 1 年后下降,但与疾病活动度的变化无关。
基于 CFFCP 的检测方法对 RA 具有高度的敏感性和特异性。包括 CCP2 阴性患者在内的早期 RA 患者出现抗 CFFCP1 抗体,表明影像学进展更大。