Chemin Karine, Klareskog Lars, Malmström Vivianne
Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden.
Curr Opin Rheumatol. 2016 Mar;28(2):181-8. doi: 10.1097/BOR.0000000000000253.
Rheumatoid arthritis (RA) is not a homogenous disease entity but a syndrome with different causes and abnormalities with shared clinical manifestations. One major subset is anticitrullinated protein antibody (ACPA)-positive RA, which represents the larger fraction of RA patients and where autoantibodies and HLA class II association implicate an autoimmune condition. In the past few years, the specificity of the ACPA response and the possibility to subdivide patients based on ACPA subgroups have received much attention whereas the effector functions of the autoantibodies and underlying lymphocytes have not.
The review, based on HLA, will discuss the generation of the autoreactive citrulline-specific T-cell repertoire, highlight our current understanding of T-cell specificities and effector functions of both the T cells and ACPAs.
Dividing RA into subsets has only influenced clinical practice to a limited degree, that is, by indicating a better response to therapies modulating adaptive immunity, such as rituximab, in the ACPA+ disease subset. A more detailed understanding of the immune reactions underlying various subsets of RA may, however, change our view on RA therapeutics and prevention with the assumption that autoimmune variants of RA should be both curable and preventable.
综述目的：类风湿关节炎（RA）并非一种同质的疾病实体，而是一种具有不同病因和异常情况但临床表现相同的综合征。一个主要亚组是抗瓜氨酸化蛋白抗体（ACPA）阳性的类风湿关节炎，这在类风湿关节炎患者中占较大比例，其中自身抗体与人类白细胞抗原（HLA）II类的关联提示存在自身免疫状况。在过去几年中，ACPA反应的特异性以及根据ACPA亚组对患者进行细分的可能性受到了广泛关注，而自身抗体和相关淋巴细胞的效应功能却未得到重视。
最新发现：本综述将基于HLA探讨自身反应性瓜氨酸特异性T细胞库的产生，强调我们目前对T细胞特异性以及T细胞和ACPA的效应功能的理解。
总结：将类风湿关节炎分为不同亚组仅在有限程度上影响了临床实践，即表明在ACPA阳性疾病亚组中对调节适应性免疫的疗法（如利妥昔单抗）反应更好。然而，假设类风湿关节炎的自身免疫变体应是可治愈和可预防的，那么对类风湿关节炎不同亚组潜在免疫反应的更详细了解可能会改变我们对类风湿关节炎治疗和预防的看法。
