Hill Jonathan A, Al-Bishri Jamal, Gladman Dafna D, Cairns Ewa, Bell David A
Department of Medicine, Division of Rheumatology, University of Western Ontario, London, Ontario, Canada.
J Rheumatol. 2006 Nov;33(11):2115-9. Epub 2006 Aug 15.
Autoantibodies that bind citrullinated antigens are a sensitive and specific marker for rheumatoid arthritis (RA). While synthetic cyclic citrullinated peptides (CCP) are typically used to identify these antibodies, little is known about antibody reactivity to the predominant citrullinated protein found in the inflamed synovium, citrullinated fibrinogen (CitFib). We assessed the prevalence of anti-CitFib antibodies in patients with various rheumatic diseases.
In total, 65 patients with established RA and 63 patients with other rheumatic diseases were tested for serum IgM rheumatoid factor (RF), IgG anti-CCP2, and IgG anti-CitFib antibodies. This cohort was used to determine optimal positive cutoff values for antibody reactivity to CitFib through receiver operating characteristic curve analysis. The specificity of these assays was confirmed with sera from 49 patients with psoriatic arthritis.
Antibodies to both citrullinated antigens were identified in the majority of RA patients tested. The overall sensitivity and specificity of the assays were: CCP 82%, 96%, CitFib 75%, 98%, and IgM RF 80%, 64%, respectively. All but one patient that was positive for CitFib was also positive for CCP2, and close to half the RF-negative RA patients were positive for CitFib and CCP2.
These results suggest that autoimmunity to CitFib is common in patients with RA and may play a role in disease pathogenesis.
结合瓜氨酸化抗原的自身抗体是类风湿关节炎（RA）的一种敏感且特异的标志物。虽然合成环瓜氨酸肽（CCP）通常用于识别这些抗体，但对于炎症滑膜中主要的瓜氨酸化蛋白——瓜氨酸化纤维蛋白原（CitFib）的抗体反应性却知之甚少。我们评估了各种风湿性疾病患者中抗CitFib抗体的患病率。
总共对65例确诊RA患者和63例其他风湿性疾病患者检测了血清IgM类风湿因子（RF）、IgG抗CCP2和IgG抗CitFib抗体。通过受试者工作特征曲线分析，利用该队列确定抗体对CitFib反应性的最佳阳性临界值。用49例银屑病关节炎患者的血清证实了这些检测方法的特异性。
在大多数接受检测的RA患者中均检测到针对两种瓜氨酸化抗原的抗体。这些检测的总体敏感性和特异性分别为：CCP 82%、96%，CitFib 75%、98%，IgM RF 80%、64%。除1例患者外，所有CitFib阳性患者CCP2也呈阳性，近一半RF阴性的RA患者CitFib和CCP2呈阳性。
这些结果表明，RA患者中对CitFib的自身免疫很常见，可能在疾病发病机制中起作用。
