Dekkers Jacqueline, Toes René E M, Huizinga Tom W J, van der Woude Diane
Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Curr Opin Rheumatol. 2016 May;28(3):275-81. doi: 10.1097/BOR.0000000000000277.
This review provides an update on the recent discoveries on the role of anticitrullinated protein antibodies (ACPA) in early rheumatoid arthritis (RA).
RA is characterized by an immune response against posttranslationally modified proteins, in particular citrullinated proteins. Recent studies have found that the ACPA response matures shortly before clinical disease manifests itself and is characterized by an increase in titre, isotype switching, antigen-recognition profile, and a change in the Fc-glycosylation pattern. To date, many citrullinated autoantigens have been identified and novel studies suggest that the human leucocyte antigen class II locus may directly influence the maturation of the ACPA response via antigen-specific T cells. Clinical studies have demonstrated that effective treatment of arthritis can lead to reduced ACPA levels or a change in composition of ACPA. In addition to ACPA, autoantibodies targeting other posttranslational modifications have been identified and may be associated with disease prognosis.
Key studies have demonstrated that autoimmunity against citrullinated proteins is already present in preclinical RA and matures over time. Future studies are required to reveal whether autoantibodies and the B cells that produce them play a role in disease development or can function as biomarkers for disease maturation.
本综述提供了抗瓜氨酸化蛋白抗体（ACPA）在早期类风湿关节炎（RA）中作用的最新研究发现。
RA的特征是针对翻译后修饰蛋白，特别是瓜氨酸化蛋白的免疫反应。最近的研究发现，ACPA反应在临床疾病出现前不久成熟，其特征为滴度增加、亚型转换、抗原识别谱以及Fc糖基化模式的改变。迄今为止，已鉴定出许多瓜氨酸化自身抗原，新的研究表明人类白细胞抗原II类基因座可能通过抗原特异性T细胞直接影响ACPA反应的成熟。临床研究表明，关节炎的有效治疗可导致ACPA水平降低或ACPA组成改变。除ACPA外，已鉴定出针对其他翻译后修饰的自身抗体，且可能与疾病预后相关。
关键研究表明，针对瓜氨酸化蛋白的自身免疫在临床前期RA中就已存在，并随时间成熟。未来需要开展研究以揭示自身抗体及其产生的B细胞是否在疾病发展中起作用或能否作为疾病成熟的生物标志物。
