Rheumatology Unit, Department of Medicine, KarolinskaInstitutet/Karolinska University Hospital, Stockholm, Sweden.
Curr Opin Rheumatol. 2014 Jan;26(1):72-9. doi: 10.1097/BOR.0000000000000016.
To describe recent progress concerning rheumatoid arthritis (RA)-associated autoantibodies, in particular antibodies to citrullinated proteins antigens.
An increasingly diverse and RA-associated repertoire of antibodies has been defined over the last few years. These antibodies are preferentially, but not exclusively, reactive with posttranslationally modified antigens. Citrullinated antigens are the most common targets, but also other modifications including homocitrullination (carbamylation) are recognized. These antibodies display varying degrees of cross-reactivity, and both broadly cross-reactive and monoreactive antibodies are present. Progress, described in this review, has been made both concerning mechanisms behind the generation of these antibodies and concerning their effector functions.
Several different triggering mechanisms are involved in forming an antibody repertoire that evolves before the onset of clinical disease, and where antibodies with different specificities may interact directly or indirectly with target organs in causing different arthritis-associated symptoms. The increasing understanding of the role of adaptive and specific immunity in RA creates opportunities for a new generation of interventions.
描述类风湿关节炎(RA)相关自身抗体,特别是抗瓜氨酸化蛋白抗原抗体的最新进展。
近年来,已确定了越来越多样化且与 RA 相关的抗体库。这些抗体优先但并非排他性地与翻译后修饰的抗原反应。瓜氨酸化抗原是最常见的靶标,但也识别其他修饰,包括同型瓜氨酸化(氨甲酰化)。这些抗体显示出不同程度的交叉反应性,既有广泛交叉反应性的抗体,也有单反应性的抗体。本综述描述了在这些抗体产生的机制及其效应功能方面取得的进展。
在临床疾病发生之前,形成一个抗体库涉及几种不同的触发机制,其中具有不同特异性的抗体可能直接或间接与靶器官相互作用,导致不同的关节炎相关症状。对适应性和特异性免疫在 RA 中的作用的认识不断加深,为新一代干预措施创造了机会。