A combination of autoantibodies to cyclic citrullinated peptide (CCP) and HLA-DRB1 locus antigens is strongly associated with future onset of rheumatoid arthritis
A combination of autoantibodies to cyclic citrullinated peptide (CCP) and HLA-DRB1 locus antigens is strongly associated with future onset of rheumatoid arthritis
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DOI：
10.1186/ar1187
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发表时间：
2004-01-01
影响因子：
4.9
通讯作者：
Dahlqvist, SR
中科院分区：
文献类型：
--
作者：
Berglin, E;Padyukov, L;Dahlqvist, SR
抗环瓜氨酸肽（CCP）和类风湿因子（RF）的抗体已被证明可在类风湿关节炎（RA）发病前数年出现。在瑞典北方健康与疾病研究队列中进行了一项巢式病例对照研究，以分析随后发生RA的个体中是否存在共享表位（SE）基因（定义为HLA-DRB 1 * 0404或DRB 1 * 0401）以及抗CCP抗体和RF。RA患者是从献血者中确定的，这些献血者的样本是在症状发作前几年收集的。从同一队列中随机选择年龄、性别和采样日期匹配的对照组。用聚合酶链反应序列特异性引物鉴定SE基因。使用酶免疫测定法测定抗CCP 2抗体和RF。59名RA患者被确定为献血者，在出现RA症状之前的中位提前时间为2.0年（四分位数范围为0.9 - 3.9年）。SE作为RA诊断指标的敏感性为60%，特异性为64%。抗CCP抗体的相应数字分别为37%和98%，RF的相应数字分别为17 - 42%和94%。在逻辑回归分析中，SE（比值比[OR] = 2.35）、抗CCP抗体（OR = 15.9）和IgA-RF（OR = 6.8）显著预测RA。在联合模型分析中，抗CCP抗体联合SE具有最高OR（66.8，95%置信区间8.3 - 539.4）与不具有SE的抗CCP抗体相比，预测RA（OR = 25.01，95%置信区间2.8 - 222.2）或SE无抗CCP抗体（OR = 1.9，95%置信区间0.9 - 4.2）。这项研究表明，抗CCP抗体的存在与SE基因携带与未来RA发展的相对风险非常高。
Antibodies against cyclic citrullinated peptide (CCP) and rheumatoid factors (RFs) have been demonstrated to predate the onset of rheumatoid arthritis ( RA) by years. A nested case control study was performed within the Northern Sweden Health and Disease study cohort to analyse the presence of shared epitope ( SE) genes, defined as HLA-DRB1* 0404 or DRB1* 0401, and of anti-CCP antibodies and RFs in individuals who subsequently developed RA. Patients with RA were identified from among blood donors whose samples had been collected years before the onset of symptoms. Controls matched for age, sex, and date of sampling were selected randomly from the same cohort. The SE genes were identified by polymerase chain reaction sequence-specific primers. Anti-CCP2 antibodies and RFs were determined using enzyme immunoassays. Fifty-nine individuals with RA were identified as blood donors, with a median antedating time of 2.0 years interquartile range 0.9 - 3.9 years) before presenting with symptoms of RA. The sensitivity for SE as a diagnostic indicator for RA was 60% and the specificity was 64%. The corresponding figures for anti-CCP antibodies were 37% and 98%, and for RFs, 17 - 42% and 94%, respectively. In a logistic regression analysis, SE ( odds ratio [OR] = 2.35), anti-CCP antibodies ( OR = 15.9), and IgA-RF ( OR = 6.8) significantly predicted RA. In a combination model analysis, anti-CCP antibodies combined with SE had the highest OR (66.8, 95% confidence interval 8.3 - 539.4) in predicting RA, compared with anti-CCP antibodies without SE ( OR = 25.01, 95% confidence interval 2.8 - 222.2) or SE without anti-CCP antibodies ( OR = 1.9, 95% confidence interval 0.9 - 4.2). This study showed that the presence of anti-CCP antibodies together with SE gene carriage is associated with a very high relative risk for future development of RA.