Rheumatoid arthritis is a heterogeneous disease, which can be, based on data combining genetic risk factors and autoantibodies, sub-classified into ACPA-positive and -negative RA. Presence of ACPA and RF as well as rising CRP-levels in some patients years before onset of clinical symptoms indicate that relevant immune responses for RA development are initiated very early. ACPA are highly specific for RA, whereas RF can also be found among healthy (elderly) individuals and patients with other autoimmune diseases or infection. The most important genetic risk factor for RA development, the shared epitope alleles, resides in the MHC class II region. Shared epitope alleles, however, only predispose to the development of ACPA-positive RA. Smoking is thus far the most important environmental risk factor associated with the development of RA. Studies on synovitis have shown the importance not only of adaptive but also of innate immune responses. In summary of the various results from immunological changes in blood and synovial tissue, the extension of the immune response from a diffuse myeloid to a lympho-myeloid inflammation appears to be associated with a more successful therapeutic response to biologics. With respect to advances in synovitis research, new targets for treatment against pathological subsets of immune cells or fibroblasts are already on the horizon. However, alternative strategies involving the microbiome may play an important role as well and research in this field is growing rapidly.

中文翻译：

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类风湿性关节炎的病因。

类风湿性关节炎是一种异质性疾病，根据遗传风险因素和自身抗体的数据，可将其细分为 ACPA 阳性和阴性 RA。ACPA 和 RF 的存在以及一些患者在临床症状出现前数年的 CRP 水平升高表明，RA 发展的相关免疫反应很早就开始了。ACPA 对 RA 具有高度特异性，而 RF 也可以在健康（老年人）个体和患有其他自身免疫性疾病或感染的患者中发现。RA 发展的最重要遗传风险因素，共享表位等位基因，位于 MHC II 类区域。然而，共享表位等位基因仅易于发展为 ACPA 阳性 RA。迄今为止，吸烟是与 RA 发展相关的最重要的环境风险因素。对滑膜炎的研究表明，不仅适应性免疫反应而且先天免疫反应也很重要。总结血液和滑膜组织免疫学变化的各种结果，免疫反应从弥漫性骨髓炎症扩展到淋巴-骨髓炎症似乎与对生物制剂更成功的治疗反应有关。关于滑膜炎研究的进展，针对免疫细胞或成纤维细胞病理亚群的治疗新靶点已经出现。然而，涉及微生物组的替代策略也可能发挥重要作用，该领域的研究正在迅速发展。免疫反应从弥漫性骨髓炎症扩展到淋巴-骨髓炎症似乎与对生物制剂更成功的治疗反应有关。关于滑膜炎研究的进展，针对免疫细胞或成纤维细胞病理亚群的治疗新靶点已经出现。然而，涉及微生物组的替代策略也可能发挥重要作用，该领域的研究正在迅速发展。免疫反应从弥漫性骨髓炎症扩展到淋巴-骨髓炎症似乎与对生物制剂更成功的治疗反应有关。关于滑膜炎研究的进展，针对免疫细胞或成纤维细胞病理亚群的治疗新靶点已经出现。然而，涉及微生物组的替代策略也可能发挥重要作用，该领域的研究正在迅速发展。