Antibodies to citrullinated proteins (ACPA), i.e., to peptides posttranslationally modified by the conversion of arginine to citrulline, are specific serological markers for rheumatoid arthritis (RA). Studies on anticitrulline immunity, summarized in this review, demonstrate that the criterion-based syndrome RA should be subdivided into at least two distinct subsets (ACPA-positive and ACPA-negative disease). A new etiological model is proposed for ACPA-positive RA, built on MHC class II-dependent activation of adaptive immunity. Fundamentals of this model include the following: (a) ACPA antedate onset of arthritis; (b) ACPA may aggravate arthritis in rodents; (c) ACPA are triggered in the context of genes that confer susceptibility to RA (HLA-DRB1 SE) and by environmental agents triggering RA (smoking or bacterial stimuli); (d) ACPA may complex with citrullinated proteins present in target tissue as part of a multistep process for arthritis development. The model provides a new basis for molecular studies on the pathogenesis of ACPA-positive arthritis.

中文翻译：

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类风湿关节炎对瓜氨酸化蛋白的免疫。

瓜氨酸化蛋白（ACPA）的抗体，即通过精氨酸转化为瓜氨酸转化后修饰的肽的抗体，是类风湿关节炎（RA）的特异性血清标志物。综述中的抗瓜氨酸免疫研究表明，基于标准的综合症应至少分为两个亚群（ACPA阳性和ACPA阴性）。提出了针对ACPA阳性RA的新病因模型，该模型建立在MHC II类依赖性自适应免疫激活的基础上。该模型的基本原理包括：（a）ACPA先于关节炎发作；（b）ACPA可能加剧啮齿动物的关节炎；（c）ACPA在赋予RA易感性的基因（HLA-DRB1 SE）的背景下触发，并由触发RA的环境因素（吸烟或细菌刺激）触发；（d）ACPA可能与靶组织中存在的瓜氨酸化蛋白复合，这是关节炎发展的多步骤过程的一部分。该模型为ACPA阳性关节炎发病机理的分子研究提供了新的依据。