Kawabata Kimito, Yamamoto Kazuhiko
Division of Allergy and Rheumatology, Department of Medicine, University of Tokyo Hospital.
Clin Calcium. 2009 Mar;19(3):303-9.
Rheumatoid arthritis is a chronic inflammatory polyarthritis and is thought to be an autoimmune, multifactorial and polygenic disease. Recent studies have uncovered many important players in the pathogenesis of rheumatoid arthritis. Immune cells, mesenchymal cells, and bone-associated cells are all involved in the pathogenesis and are closely related with each other. The genetic predisposition to rheumatoid arthritis is confirmed by many family studies and HLA association studies. Genome-wide disease association studies identified genetic risk foci, such as HLA-DRB1, PADI4, and PTPN22. In addition to the genetic contribution, environmental factors are increasingly recognized. Many studies revealed that smoking is a risk factor for rheumatoid arthritis. The role of B and T lymphocytes in the pathogenesis has been reevaluated by biological agents such as rituximab (anti-CD20 antibody) and abatacept (CTLA4-Ig) , respectively. T cells in rheumatoid arthritis have been shown to have the altered level of surface molecules such as CD28, cytokine pattern shift, and shortened telomere lengths. Moreover, telomere loss is recognized not only in lymphocytes but also in hematopoietic progenitor cells. This phenomenon and the presence of rheumatoid-specific anti-citrullinated protein antibodies are reported to be associated with HLA haplotypes.
类风湿性关节炎是一种慢性炎症性多关节炎，被认为是一种自身免疫性、多因素和多基因疾病。最近的研究揭示了类风湿性关节炎发病机制中的许多重要因素。免疫细胞、间充质细胞和骨相关细胞均参与发病机制，且彼此密切相关。许多家族研究和HLA关联研究证实了类风湿性关节炎的遗传易感性。全基因组疾病关联研究确定了遗传风险位点，如HLA-DRB1、PADI4和PTPN22。除了遗传因素外，环境因素也越来越受到认可。许多研究表明吸烟是类风湿性关节炎的一个危险因素。利妥昔单抗（抗CD20抗体）和阿巴西普（CTLA4-Ig）等生物制剂分别重新评估了B和T淋巴细胞在发病机制中的作用。类风湿性关节炎中的T细胞已被证明其表面分子如CD28的水平发生改变、细胞因子模式转变以及端粒长度缩短。此外，不仅在淋巴细胞中，而且在造血祖细胞中也发现了端粒缺失。据报道，这种现象以及类风湿特异性抗瓜氨酸化蛋白抗体的存在与HLA单倍型有关。
