Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, Japan.
Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Arthritis Res Ther. 2020 Oct 19;22(1):248. doi: 10.1186/s13075-020-02351-4.
The anti-cyclic citrullinated peptide (CCP) antibody is a diagnostic biomarker of rheumatoid arthritis (RA). However, some non-RA connective tissue disease (CTD) patients also test positive for the anti-CCP antibody and, thus, may ultimately develop RA. We retrospectively investigated whether anti-CCP-positive non-RA CTD patients developed RA and attempted to identify factors that may differentiate RA-overlapping CTD from pure CTD.
In total, 842 CTD patients with a primary diagnosis that was not RA were selected from our CTD database as of December 2012. Anti-CCP antibody titers were obtained from a retrospective chart review or measured using stored sera. RA was diagnosed according to the 1987 revised American College of Rheumatology classification criteria. Thirty-three anti-CCP-positive non-RA CTD patients were retrospectively followed up for the development of RA. Bone erosions on the hands and feet were assessed by X-ray. Citrullination dependency was evaluated by an in-house ELISA, the HLA-DRB1 allele was typed, and the results obtained were then compared between RA-overlapping and non-RA anti-CCP-positive CTD patients.
Two out of 33 anti-CCP-positive CTD patients (6.1%) developed RA during a mean follow-up period of 8.9 years. X-rays were examined in 27 out of the 33 patients, and only one (3.7%) showed bone erosions. The frequency of the HLA-DRB1 shared epitope (SE) and anti-CCP antibody titers were both significantly higher in anti-CCP-positive RA-overlapping CTD patients than in anti-CCP-positive non-RA CTD patients, while no significant differences were observed in citrullination dependency.
Anti-CCP-positive non-RA CTD patients rarely developed RA. HLA-DRB1 SE and anti-CCP antibody titers may facilitate the differentiation of RA-overlapping CTD from anti-CCP-positive non-RA CTD.
抗环瓜氨酸肽（CCP）抗体是类风湿关节炎（RA）的诊断生物标志物。然而，一些非 RA 的结缔组织疾病（CTD）患者的抗 CCP 抗体也呈阳性，因此最终可能发展为 RA。我们回顾性研究了抗 CCP 阳性的非 RA CTD 患者是否会发展为 RA，并试图确定可能区分重叠性 RA-CTD 和单纯性 CTD 的因素。
我们从 2012 年 12 月的 CTD 数据库中选择了 842 例原发性诊断非 RA 的 CTD 患者。通过回顾病历或检测储存的血清获得抗 CCP 抗体滴度。根据 1987 年修订的美国风湿病学会分类标准诊断 RA。对 33 例抗 CCP 阳性的非 RA CTD 患者进行回顾性随访，以观察 RA 的发生。通过 X 射线评估手和脚的骨侵蚀。通过内部 ELISA 评估瓜氨酸依赖性，对 HLA-DRB1 等位基因进行分型，并比较重叠性 RA-CTD 和非重叠性 RA-CCP 阳性 CTD 患者之间的结果。
在平均 8.9 年的随访期间，33 例抗 CCP 阳性 CTD 患者中有 2 例（6.1%）发展为 RA。在 33 例患者中，有 27 例接受了 X 射线检查，只有 1 例（3.7%）显示骨侵蚀。重叠性 RA-CTD 患者的 HLA-DRB1 共享表位（SE）和抗 CCP 抗体滴度均显著高于非重叠性 RA-CCP 阳性 CTD 患者，而瓜氨酸依赖性无显著差异。
抗 CCP 阳性的非 RA CTD 患者很少发展为 RA。HLA-DRB1 SE 和抗 CCP 抗体滴度可能有助于区分重叠性 RA-CTD 和抗 CCP 阳性非 RA-CTD。
