van der Linden Michael P M, van der Woude Diane, Ioan-Facsinay Andreea, Levarht E W Nivine, Stoeken-Rijsbergen Gerrie, Huizinga Tom W J, Toes René E M, van der Helm-van Mil Annette H M
Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Arthritis Rheum. 2009 Aug;60(8):2232-41. doi: 10.1002/art.24716.
Autoantibodies such as rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPAs) determined by testing with second-generation anti-cyclic citrullinated peptide (anti-CCP-2) are frequently measured in clinical practice because of their association with disease outcome in undifferentiated arthritis (UA) and rheumatoid arthritis (RA). Recently, 2 new ACPA tests were developed: third-generation anti-CCP (anti-CCP-3) and anti-modified citrullinated vimentin (anti-MCV) autoantibody tests. To facilitate the decision on which autoantibody to test in daily practice, this study evaluated the capability of these autoantibodies and combinations of them to predict 3 outcome measures: progression from UA to RA, the rate of joint destruction in RA, and the chance of achieving sustained disease-modifying antirheumatic drug (DMARD)-free remission in RA.
Patients with UA (n=625) were studied for whether UA progressed to RA after 1 year. Patients with RA (n=687) were studied for whether sustained DMARD-free remission was achieved and for the rate of joint destruction during a median followup of 5 years. Positive predictive values (PPVs) for RA development and for associations with the disease course in RA were compared between single tests (anti-CCP-2, anti-CCP-3, anti-MCV, and RF) and between combinations of these tests.
Among the single tests performed in patients with UA, anti-CCP-2 tended to have the highest PPV for RA development (67.1%), but the 95% confidence intervals of the other tests overlapped. Among the single tests in patients with RA, all 4 tests showed comparable associations with the rate of joint destruction and with the achievement of remission. In both ACPA-positive and ACPA-negative RA, the presence of RF was not associated with more joint destruction. For all outcome measures, performing combinations of 2 or 3 autoantibody tests did not increase the predictive accuracy compared with performing a single test.
For clinical practice, a single autoantibody test is sufficient for risk estimation in UA and RA.
类风湿因子(RF)和抗瓜氨酸化蛋白自身抗体(ACPA,通过第二代抗环瓜氨酸肽检测[抗CCP-2]测定)等自身抗体,因其与未分化关节炎(UA)和类风湿关节炎(RA)的疾病转归相关,在临床实践中经常被检测。最近,开发了2种新的ACPA检测方法:第三代抗CCP(抗CCP-3)和抗修饰瓜氨酸波形蛋白(抗MCV)自身抗体检测。为便于在日常实践中决定检测哪种自身抗体,本研究评估了这些自身抗体及其组合预测3种转归指标的能力:从UA进展为RA、RA中的关节破坏率,以及在RA中实现持续停用改善病情抗风湿药(DMARD)缓解的可能性。
对625例UA患者进行研究,观察1年后UA是否进展为RA。对687例RA患者进行研究,观察是否实现持续停用DMARD缓解,以及在中位随访5年期间的关节破坏率。比较单项检测(抗CCP-2、抗CCP-3、抗MCV和RF)之间以及这些检测组合之间RA发生的阳性预测值(PPV)和与RA病程的相关性。
在对UA患者进行的单项检测中,抗CCP-2对RA发生的PPV往往最高(67.1%),但其他检测的95%置信区间相互重叠。在对RA患者进行的单项检测中,所有4种检测与关节破坏率和缓解的实现均显示出相当的相关性。在ACPA阳性和ACPA阴性的RA中,RF的存在均与更多关节破坏无关。对于所有转归指标,与进行单项检测相比,进行2种或3种自身抗体检测的组合并未提高预测准确性。
对于临床实践,单项自身抗体检测足以对UA和RA进行风险评估。