The development of rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPAs) can be observed years prior to clinical diagnosis of rheumatoid arthritis (RA). Nevertheless, the interaction between these two autoantibodies and their combined effect on development of RA is unclear. We measured RF, cytokines, and ACPA subtypes in serial pre-clinical serum samples collected from 83 US veterans who all developed RA. Levels of cytokines and ACPAs were compared between the following groups: anti-cyclic citrullinated peptide (anti-CCP)-/RF- (double negative), anti-CCP+/RF-, anti-CCP-/RF+, or anti-CCP+/RF+ (double-positive). The double-positive subgroup had significantly higher levels of 20 inflammatory cytokines and 29 ACPA reactivities, and the shortest interval, 1.3 years, between the preclinical sample timepoint and diagnosis of RA. Thus, the combined presence of ACPAs and RF is associated with a more rapid progression to RA, suggesting that anti-CCP+/RF+ individuals have a more advanced preclinical disease state and that the onset of RA may be imminent.

中文翻译：

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抗瓜氨酸化蛋白抗体和类风湿因子的组合与全身炎症介质的增加和从临床前类风湿关节炎到临床类风湿关节炎的更快发展有关。

类风湿因子（RF）和/或抗瓜氨酸化蛋白抗体（ACPA）的发展可在临床诊断类风湿关节炎（RA）之前的数年内观察到。然而，尚不清楚这两种自身抗体之间的相互作用及其对RA发生的综合作用。我们测量了从83位均患有RA的美国退伍军人中收集的临床前血清样品中的RF，细胞因子和ACPA亚型。在以下组之间比较了细胞因子和ACPA的水平：抗环瓜氨酸肽（anti-CCP）-/ RF-（双阴性），anti-CCP + / RF-，anti-CCP- / RF +或anti-CCP + / RF +（双正）。双阳性亚组具有较高的20种炎性细胞因子水平和29种ACPA反应性，并且在临床前样本时间点与RA诊断之间的最短间隔为1.3年。