Third Department of Internal Medicine, Faculty of Medicine, Tokyo Medical University, 7-6-1 Nishishinjuku, Shinjuku, Tokyo, 160-0023 Japan.
Clin Exp Rheumatol. 2009 Nov-Dec;27(6):989-92.
Previous studies have demonstrated that immune complexes (ICs) may be involved in the pathogenesis of rheumatoid arthritis (RA). However, autoantigens contained in rheumatoid ICs remain to be elucidated. In the present study, we investigated whether the peptides captured by C1q and monoclonal rheumatoid factor (mRF), presumably associated with ICs, were citrullinated in synovial fluids from patients with RA.
Sixteen rheumatoid arthritis synovial fluids (RASFs), 7 osteoarthritis synovial fluids (OASFs), and 20 sera from RA patients were used for experiments. ICs were measured using commercially available kits based on the C1q-binding (C1q-IC) and mRF-binding (mRF-IC) assays. Citrullination of the peptides captured by C1q and mRF was detected by anti-modified citrulline antibody (Senshu Ab) after chemical modification.
There was a significant correlation between levels of citrullination of C1q-binding peptides and those of mRF-binding peptides in RASFs (r=0.77), both of which were significantly higher than those in OASFs. No citrullinated Ags captured by C1q and mRF were detected in sera from patients with RA.
We have demonstrated the presence of citrullinated Ags as C1q- and mRF-binding peptides in RASF. We suggest that citrullinated Ags may contribute to the pathogenesis of RA through IC formation in the joint.
先前的研究表明,免疫复合物(ICs)可能参与了类风湿关节炎(RA)的发病机制。然而,类风湿 IC 中包含的自身抗原仍有待阐明。在本研究中,我们研究了类风湿关节炎患者的滑液中,是否存在与 IC 相关的被 C1q 和单克隆类风湿因子(mRF)捕获的肽发生瓜氨酸化。
使用了 16 份类风湿关节炎滑液(RASFs)、7 份骨关节炎滑液(OASFs)和 20 份类风湿关节炎患者的血清进行实验。使用基于 C1q 结合(C1q-IC)和 mRF 结合(mRF-IC)测定的商业试剂盒来测量 IC。通过化学修饰后,用抗修饰瓜氨酸抗体(Senshu Ab)检测 C1q 和 mRF 捕获的肽的瓜氨酸化。
RASFs 中 C1q 结合肽和 mRF 结合肽的瓜氨酸化水平存在显著相关性(r=0.77),两者均显著高于 OASFs。在 RA 患者的血清中未检测到被 C1q 和 mRF 捕获的瓜氨酸化抗原。
我们已经证明了 C1q 和 mRF 结合肽中存在瓜氨酸化抗原,这些抗原可能通过关节中 IC 的形成而导致 RA 的发病机制。