Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Center for Clinical Research Dalarna, Uppsala University, Uppsala, Sweden.
Clin Exp Immunol. 2021 Jun;204(3):344-351. doi: 10.1111/cei.13591. Epub 2021 Mar 24.
Autoantibodies related to rheumatoid arthritis (RA), such as anti-citrullinated protein antibodies (ACPA), are often detectable in the preclinical period years before arthritis onset. However, events triggering arthritis development remain incompletely known. We aimed to determine whether ACPA isotype levels are prognostic for arthritis development in patients presenting with immunoglobulin (Ig)G ACPA and musculoskeletal pain. Study participants (n = 82) had musculoskeletal pain of any sort and duration and a positive IgG ACPA test. None of the patients had arthritis upon clinical examination at baseline, but during follow-up (mean = 6 years), 48% developed at least one arthritic joint. IgG, IgA, IgM and secretory component (SC)-containing ACPA was measured in longitudinally collected serum samples. Cox regression analysis was performed to test the prognostic value of baseline antibody levels and changes over time. All analysed ACPA isotype levels were associated with arthritis development in univariable Cox regression analysis. In multivariable analysis, baseline SC ACPA levels were independently prognostic for arthritis development in multivariable analysis [hazard ratio (HR) = 1·006, 95% confidence interval (CI) = 1·001-1·010, P = 0·012]. There were no significant changes in ACPA isotype levels over time, and no significant association between changes over time and arthritis development. In this prospective longitudinal study, baseline serum SC ACPA levels, but neither IgG, IgA nor IgM ACPA are prognostic for future arthritis development. Repeated measurement of ACPA isotypes do not bring additional prognostic value. The results reinforce a mucosal connection in RA development and encourage further exploration of the mechanisms underlying secretory ACPA formation as a trigger for arthritis development.
与类风湿关节炎 (RA) 相关的自身抗体，如抗瓜氨酸蛋白抗体 (ACPA)，常在关节炎发病前数年的临床前阶段即可检测到。然而，触发关节炎发展的事件仍不完全清楚。我们旨在确定在出现免疫球蛋白 (Ig)G ACPA 和肌肉骨骼疼痛的患者中，ACPA 同种型水平是否与关节炎发展有关。研究参与者（n=82）有任何类型和持续时间的肌肉骨骼疼痛，且 IgG ACPA 检测呈阳性。在基线临床检查时，没有患者出现关节炎，但在随访期间（平均=6 年），48%的患者至少出现了一个关节炎关节。在纵向收集的血清样本中测量了 IgG、IgA、IgM 和含有分泌成分 (SC) 的 ACPA。进行 Cox 回归分析以检验基线抗体水平和随时间变化的预后价值。在单变量 Cox 回归分析中，所有分析的 ACPA 同种型水平与关节炎的发展相关。在多变量分析中，基线 SC ACPA 水平与关节炎的发生独立相关[风险比 (HR) = 1.006，95%置信区间 (CI) = 1.001-1.010，P=0.012]。在随时间的变化过程中，ACPA 同种型水平没有显著变化，且随时间的变化与关节炎的发展之间没有显著关联。在这项前瞻性纵向研究中，基线血清 SC ACPA 水平，但 IgG、IgA 或 IgM ACPA 均与未来关节炎的发展无关。ACPA 同种型的重复测量没有带来额外的预后价值。这些结果强化了 RA 发病过程中黏膜连接的作用，并鼓励进一步探索作为关节炎发病触发因素的分泌型 ACPA 形成的机制。
