Anti-citrullinated protein/peptide autoantibodies in association with genetic and environmental factors as indicators of disease outcome in rheumatoid arthritis
Anti-citrullinated protein/peptide autoantibodies in association with genetic and environmental factors as indicators of disease outcome in rheumatoid arthritis
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DOI：
10.1016/j.autrev.2009.04.006
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发表时间：
2010-01-01
影响因子：
13.6
通讯作者：
Szekanecz, Zoltan
中科院分区：
文献类型：
--
作者：
Szodoray, Peter;Szabo, Zoltan;Szekanecz, Zoltan
抗瓜氨酸蛋白/肽抗体 (ACPA) 最近已成为类风湿关节炎 (RA) 敏感且特异的血清学标志物，为 RA 实验室诊断中的类风湿因子 (RF) 测试提供了更好的替代方案。瓜氨酸化是精氨酸通过脱亚胺作用进行的翻译后修饰，生理上发生在细胞凋亡、炎症或角化过程中。已证实 RA 滑膜中存在多种瓜氨酸蛋白。瓜氨酸表位作为靶标的鉴定导致了第一代和后来的第二代抗环瓜氨酸肽（抗 CCP）抗体测定的发展。抗Sa抗体十年前就已被鉴定出来；然而，最近的研究证实，抗 Sa 是针对瓜氨酸波形蛋白的。 ACPA 的测定可能具有重要的预后意义，因为 ACPA 的产生可能比 RA 临床症状的出现早数年。患有早期未分化关节炎的 ACPA(+) 个体患 RA 的风险可能更高。 ACPA 在 RA 进展过程中具有重要的预后作用，并且还与显着的放射学进展相关。 ACPA 的产生与多种遗传易感因素有关，包括 HLA-DRB1 和 PTPN22 1858T 等位基因，以及环境和生活方式相关因素，主要是吸烟，也可能与使用口服避孕药和过量咖啡因摄入有关。因此，除了临床、放射学和遗传结果测量之外，ACPA 的评估对于评估疾病预后可能很重要，并有助于设计有效的早期治疗策略。 (C) 2009 Elsevier B.V. 保留所有权利。
Anti-citrullinated protein/peptide antibodies (ACPA) have recently emerged as sensitive and specific serological markers of rheumatoid arthritis (RA), providing superior alternative of the rheumatoid factor (RF) test in the laboratory diagnostics of RA. Citrullination is a post-translational modification of arginine by deimination, physiologically occurring during apoptosis, inflammation or keratinization. The presence of several citrullinated proteins has been demonstrated in the RA synovium. The identification of citrullinated epitopes as targets led to the development of the first and later second-generation anti-cyclic citrullinated peptide (anti-CCP) antibody assays. The anti-Sa antibody has been identified a decade ago; however, recent studies confirmed that anti-Sa is directed against citrullinated vimentin. The determination of ACPA may have important prognostic significance, since ACPA production can precede the onset of clinical RA symptoms by years. ACPA(+) individuals with early, undifferentiated arthritis may have higher risk to develop RA. ACPA has important prognostic role during the progression of RA and it has also been associated with pronounced radiographic progression. ACPA production has been associated with several genetic predisposing factors, including HLA-DRB1 and PTPN22 1858T alleles, as well as with environmental and lifestyle-related factors, primarily smoking and possibly, the use of oral contraceptives and excessive caffeine intake. Thus, the assessment of ACPA, in addition to clinical, radiographic and genetic outcome measures may be important to assess disease prognosis and aids to design effective, early therapeutic strategies. (C) 2009 Elsevier B.V. All rights reserved.