Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
Nat Rev Rheumatol. 2012 Jan 31;8(3):144-52. doi: 10.1038/nrrheum.2011.204.
Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, and affects 0.5-1% of the population. Although it poses a considerable health problem, relatively little remains known about the disease pathogenesis and etiology. In the past decade, anti-citrullinated protein antibodies (ACPA) have emerged as suspects in the development and/or progression of RA. Citrullinated proteins--containing the amino acid citrulline, generated post-translationally from arginine--are found in the joints of patients with RA, but are not specific for the disease. This situation contrasts with the presence of ACPA, which are mostly found in individuals with RA. Intriguingly, ACPA can also be found in individuals before symptom onset. In these instances the ACPA response seems to be in its infancy, recognizing only a few citrullinated antigens and not using the full isotype repertoire. These characteristics of the ACPA response mature before clinical disease precipitates. Evidence is emerging that ACPA status can further characterize the heterogeneous RA phenotype, not only with respect to outcome, but perhaps also with respect to intervention. This Review summarizes the evolution of the ACPA response and its putative role in disease pathogenesis, as well as its relationship with clinical phenotype and diagnostic potential.
类风湿关节炎（RA）是最常见的自身免疫性疾病之一，影响着 0.5-1%的人口。尽管它构成了相当大的健康问题，但人们对这种疾病的发病机制和病因知之甚少。在过去的十年中，抗瓜氨酸化蛋白抗体（ACPA）已成为 RA 发展和/或进展的嫌疑犯。瓜氨酸化蛋白——含有氨基酸瓜氨酸，从精氨酸翻译后产生——存在于 RA 患者的关节中，但不是该疾病的特异性。这种情况与 ACPA 的存在形成对比，ACPA 主要存在于 RA 患者中。有趣的是，ACPA 也可以在症状出现前的个体中发现。在这些情况下，ACPA 反应似乎处于初期，仅识别少数瓜氨酸化抗原，并且不使用全同种型库。这些 ACPA 反应的特征在临床疾病发作之前成熟。有证据表明，ACPA 状态可以进一步描述 RA 的异质表型，不仅在预后方面，而且在干预方面也是如此。这篇综述总结了 ACPA 反应的演变及其在疾病发病机制中的潜在作用，以及它与临床表型和诊断潜力的关系。
