Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
Deutsches Zentrum für Immuntherapie, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
RMD Open. 2023 Jan;9(1). doi: 10.1136/rmdopen-2022-002705.
Events triggering disease outbreak in individuals at-risk for rheumatoid arthritis (RA at-risk) remain unclear, and the role of the various anticitrullinated protein antibody (ACPA) isotypes in this process is still to be established. We aimed to investigate the prevalence of IgA ACPA in RA at-risk individuals, their role in the transition from the RA at-risk status to RA and their dynamics during this transition.
Cross-sectional measurement of serum IgA1 and IgA2 ACPA levels was conducted in healthy controls, RA at-risk individuals and patients with RA and compared with the frequency of RA development in at risk individuals during a follow-up of 14 months. In addition, longitudinal measurements of serum IgA1 and IgA2 ACPA levels prior to, at and after the onset of RA were performed.
Approximately two-thirds of RA at-risk individuals were positive for serum IgA1 and IgA2 ACPA in levels comparable to IgG ACPA positive patients with RA. IgA1, but not IgA2 ACPA positivity was associated with the transition from the RA at-risk state to RA within the following 14 months. Interestingly, during this transition process, IgA1 ACPA levels declined at RA onset and also thereafter during the early phase of RA. This decline was confirmed in a second, independent cohort.
Both IgA1 and IgA2 ACPA are present in RA at-risk individuals, but only IgA1 ACPA are associated with the progression to RA. The observed decline in serum IgA1 ACPA levels before the onset of RA might indicate starting barrier leakiness prior to disease outbreak.
导致类风湿关节炎（RA 高危）个体发病的事件仍不清楚，各种抗瓜氨酸蛋白抗体（ACPA）同种型在这一过程中的作用仍有待确定。我们旨在研究 RA 高危个体中 IgA ACPA 的患病率、它们在从 RA 高危状态向 RA 转变中的作用及其在这一转变过程中的动态变化。
在健康对照、RA 高危个体和 RA 患者中进行血清 IgA1 和 IgA2 ACPA 水平的横断面测量，并与高危个体在 14 个月的随访期间发生 RA 的频率进行比较。此外，还对 RA 发病前、发病时和发病后进行了血清 IgA1 和 IgA2 ACPA 水平的纵向测量。
大约三分之二的 RA 高危个体的血清 IgA1 和 IgA2 ACPA 水平与 IgG ACPA 阳性的 RA 患者相当。IgA1，但不是 IgA2 ACPA 阳性与 14 个月内从 RA 高危状态向 RA 的转变有关。有趣的是，在这一转变过程中，IgA1 ACPA 水平在 RA 发病时下降，并且在 RA 的早期阶段也下降。这一下降在第二个独立的队列中得到了证实。
RA 高危个体中存在 IgA1 和 IgA2 ACPA，但只有 IgA1 ACPA 与向 RA 的进展有关。在 RA 发病前观察到的血清 IgA1 ACPA 水平下降可能表明在疾病爆发前开始出现屏障通透性增加。
