Division of Rheumatology, Department of Medicine, University of Colorado School of Medicine, 1775 Aurora Court, Aurora, CO 80045, USA. william.arend@ ucdenver.edu
Nat Rev Rheumatol. 2012 Oct;8(10):573-86. doi: 10.1038/nrrheum.2012.134. Epub 2012 Aug 21.
Multiple proven and potential risk factors for the development of rheumatoid arthritis (RA) have been identified, and represent interactions between genes and the environment. Proven risk factors include genetic influences on the function of the innate and adaptive immune systems, smoking, anti-citrullinated protein antibodies (ACPAs), and rheumatoid factors (RF). Potential risk factors include epigenetic control of gene expression, the microbiome and other environmental factors, Toll-like receptors, cytokines, and Fc receptors. Preclinical abnormalities such as circulating RF and ACPAs may occur more than 10 years prior to the onset of clinical disease. However, the precise mechanisms whereby these risk factors lead to clinical disease remain unclear. It is possible that, combined with activation of the innate immune system, a subset of ACPAs initiates the disease in the cartilage or synovium after binding to endogenous citrullinated proteins. Subsequent engagement of Fc receptors and complement activation would lead to secondary inflammation in the synovium with induction of a perpetuating cycle of chronic synovitis.
已经确定了多种类风湿关节炎 (RA) 发病的已知和潜在风险因素，这些因素代表了基因与环境之间的相互作用。已知的风险因素包括对先天和适应性免疫系统功能的遗传影响、吸烟、抗瓜氨酸化蛋白抗体 (ACPAs) 和类风湿因子 (RF)。潜在的风险因素包括基因表达的表观遗传控制、微生物组和其他环境因素、Toll 样受体、细胞因子和 Fc 受体。临床疾病发病前 10 多年可能就已经出现循环 RF 和 ACPA 等临床前异常。然而，这些风险因素导致临床疾病的确切机制仍不清楚。可能的情况是，一组 ACPA 与内源性瓜氨酸化蛋白结合后，在软骨或滑膜中引发疾病，同时激活先天免疫系统。随后 Fc 受体的参与和补体的激活将导致滑膜中的继发性炎症，并引发持续的慢性滑膜炎循环。
