Ten Brinck Robin M, van Steenbergen Hanna W, van Delft Myrthe A M, Verheul Marije K, Toes Rene E M, Trouw Leendert A, van der Helm-van Mil Annette H M
Department of Rheumatology, Leiden University Medical Centre, Leiden, the Netherlands.
Rheumatology (Oxford). 2017 Dec 1;56(12):2145-2153. doi: 10.1093/rheumatology/kex340.
Autoantibody testing is helpful for predicting the risk of progression to clinical arthritis in subjects at risk. Previous longitudinal studies have mainly selected autoantibody-positive arthralgia patients, and consequently the predictive values of autoantibodies were evaluated relative to one another. This study assessed the risks for arthritis development of ACPA, RF and/or anti-carbamylated protein antibodies (anti-CarP) in arthralgia patients considered at risk for RA by rheumatologists, based on clinical characteristics (clinically suspect arthralgia, CSA).
The baseline ACPA, RF and anti-CarP autoantibody status of 241 patients, consecutively included in the CSA cohort, was studied for risk of developing clinical arthritis during a median follow-up of 103 (interquartile range: 81-114) weeks.
Univariable associations for arthritis development were observed for ACPA, RF and anti-CarP antibodies; hazard ratios (HRs) (95% CI) were 8.5 (4.7-15.5), 5.1 (2.8-9.3) and 3.9 (1.9-7.7), respectively. In multivariable analysis, only ACPA was independently associated (HR = 5.1; 2.0-13.2). Relative to autoantibody-negative CSA patients, ACPA-negative/RF-positive patients had HRs of 2.6 (1.04-6.6), ACPA-positive/RF-negative patients 8.0 (2.4-27.4) and ACPA-positive/RF-positive patients 10.5 (5.4-20.6). Positive predictive values for development of clinical arthritis within 2 years were: 38% for ACPA-negative/RF-positive, 50% for ACPA-positive/RF-negative and 67% for ACPA-positive/RF-positive patients. Higher ACPA levels were not significantly associated with increased progression to clinical arthritis, in contrast to higher RF levels. Autoantibody levels were stable during follow-up.
ACPA conferred the highest risk for arthritis development and had an additive value to RF. However, >30% of ACPA-positive/RF-positive CSA patients did not develop arthritis during the 2-year follow-up. Thus, CSA and information on autoantibodies is insufficient for accurately identifying imminent autoantibody-positive RA.
自身抗体检测有助于预测有风险的受试者进展为临床关节炎的风险。以往的纵向研究主要选择自身抗体阳性的关节痛患者，因此对自身抗体的预测价值进行了相互比较评估。本研究基于临床特征（临床疑似关节痛，CSA），评估了风湿科医生认为有类风湿关节炎（RA）风险的关节痛患者中，抗环瓜氨酸肽抗体（ACPA）、类风湿因子（RF）和/或抗瓜氨酸化蛋白抗体（抗CarP）发生关节炎的风险。
对连续纳入CSA队列的241例患者的基线ACPA、RF和抗CarP自身抗体状态进行研究，观察其在中位随访103周（四分位间距：81 - 114周）期间发生临床关节炎的风险。
观察到ACPA、RF和抗CarP抗体与关节炎发生存在单变量关联；风险比（HRs）（95%置信区间）分别为8.5（4.7 - 15.5）、5.1（2.8 - 9.3）和3.9（1.9 - 7.7）。在多变量分析中，只有ACPA具有独立相关性（HR = 5.1；2.0 - 13.2）。与自身抗体阴性的CSA患者相比，ACPA阴性/RF阳性患者的HR为2.6（1.04 - 6.6），ACPA阳性/RF阴性患者为8.0（2.4 - 27.4），ACPA阳性/RF阳性患者为10.5（5.4 - 20.6）。2年内发生临床关节炎的阳性预测值分别为：ACPA阴性/RF阳性患者为38%，ACPA阳性/RF阴性患者为50%，ACPA阳性/RF阳性患者为67%。与较高的RF水平相反，较高的ACPA水平与进展为临床关节炎的增加无显著关联。随访期间自身抗体水平稳定。
ACPA赋予关节炎发生的风险最高，且对RF具有附加价值。然而，在2年随访期间，超过30%的ACPA阳性/RF阳性CSA患者未发生关节炎。因此，CSA和自身抗体信息不足以准确识别即将出现的自身抗体阳性RA。
