Independent associations of anti-cyclic citrullinated peptide antibodies and rheumatoid factor with radiographic severity of rheumatoid arthritis.
Independent associations of anti-cyclic citrullinated peptide antibodies and rheumatoid factor with radiographic severity of rheumatoid arthritis.
复制标题
抗偶然柠檬硫化肽抗体和类风湿因子与类风湿关节炎的放射学严重程度的独立关联。
DOI：
10.1186/ar2017
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发表时间：
2006
影响因子：
4.9
通讯作者：
Wilson, Anthony G
中科院分区：
文献类型：
--
作者：
Mewar, Devesh;Coote, Annabel;Moore, David J;Marinou, Ioanna;Keyworth, Jodie;Dickson, Marion C;Montgomery, Doug S;Binks, Michael H;Wilson, Anthony G
最近的几篇出版物已经确定了抗环瓜氨酸肽抗体（抗CCP）阳性类风湿性关节炎（RA）与携带共享表位（SE）等位基因之间的强相关性。虽然抗CCP抗体也与更严重的RA相关，但这是否独立于类风湿因子（RF）的问题尚未得到解决。为了确定RF、抗CCP抗体、SE状态和放射性损伤之间的关系，我们研究了一个大型的长期RA横断面队列。入组研究的个体（n = 872）均符合美国风湿病学会的RA标准，最短病程为3年，手或脚至少有一处明确的放射学侵蚀。在研究入组时，由一名肌肉骨骼放射科医生使用改良的Larsen评分对X光片进行盲法评分。抗CCP和RF水平测定采用酶联免疫吸附试验，DRB 1分型采用聚合酶链反应为基础的方法。抗CCP抗体和RF水平与放射学严重程度密切相关（P < 0.0001）。在抗CCP和RF状态分层的亚组中，发现两种抗体与放射学结局独立相关的证据（P < 0.0001）。SE等位基因与放射学严重程度的关联仅存在于RF阴性个体中。抗CCP抗体阳性与SE状态相关，有基因剂量效应的证据，在RF阴性个体中最显著（P < 0.01）。抗CCP和RF状态是RA的独立严重性因素，SE等位基因最多起次要作用。我们的数据支持这样的观点，即先前描述的SE和放射学严重程度之间的关联，特别是在RF阴性患者中，可能是间接的，并且是由于与抗CCP相关。
Several recent publications have established a strong association between anti-cyclic citrullinated peptide antibody (anti-CCP)-positive rheumatoid arthritis (RA) and carriage of shared epitope (SE) alleles. Although anti-CCP have also been associated with more severe RA, the issue of whether this is independent of rheumatoid factor (RF) has not been addressed. To identify associations between RF, anti-CCP, SE status and radiological damage, we studied a large cross-sectional cohort with longstanding RA. Individuals (n = 872) enrolled in the study all fulfilled the American College of Rheumatology criteria for RA, had a minimum disease duration of 3 years, and at least one definite radiographic erosion was present in hands or feet. Radiographs were scored blind at study entry by a single musculoskeletal radiologist using a modified Larsen's score. Anti-CCP and RF levels were determined using enzyme-linked immunosorbent assay, and DRB1 typing was performed using polymerase chain reaction based methodology. Both anti-CCP and RF levels were strongly associated with radiographic severity (P < 0.0001). In subgroups stratified for both anti-CCP and RF status, evidence of independent associations of both antibodies with radiographic outcome was found (P < 0.0001). An association of SE alleles with radiographic severity was present only in RF-negative individuals. Anti-CCP positivity was associated with SE status with evidence of a gene-dose effect, most markedly in RF-negative individuals (P < 0.01). Anti-CCP and RF status are independent severity factors for RA, with SE alleles playing at most a secondary role. Our data support the view that previously described associations between SE and radiological severity, especially in RF-negative patients, may be indirect and due to an association with anti-CCP.