共刺激分子CTLA-4的研究进展及在风湿病治疗中的应用

细胞毒T淋巴细胞抗原-4(CTLA-4)是免疫应答反应起始阶段T细胞活化的重要共同活化分子,它与T细胞表面的配体结合后可以抑制T细胞功能,使T细胞不能被激活,从而抑制免疫反应的发生。在多种风湿病中都发现有CTLA-4等位基因异常和蛋白表达异常。CTLA-4免疫球蛋白(CTLA-4 Ig)是针对CTLA-4的融合蛋白,能选择性地抑制免疫反应,改善患者的临床症状,达到控制疾病进展的目的。但目前的临床研究尚仅限于类风湿关节炎。临床研究的初步结果表明CTLA-4 Ig治疗类风湿关节炎是有效而安全的,但由于其临床应用时间短,在风湿病治疗中的作用还有待进一步的长期临床观察来证实。

Co-stimulatory molecule CTLA-4 and the potential application in treating rheumatic diseases

Rheumatic diseases are characterized by immunological dysfunction.T-cell medicated immune response plays a very important role in the development and persistence of rheumatic disease.CTLA-4 is an important co-stimulatory molecules expressed on T cells.It has inhibitory effect on T cell-mediated immune response.Plenty of evidences have demonstrated abnormalities in CTLA-4 alleles and proteins in patients with rheumatic diseases.Therefore,CTLA-4 has become an target in treating rheumatic diseases.CTLA-4Ig has been developed as an fusion protein which is composed of extrA-cellular domain of human CTLA-4 and the Fc fragment of human IgG1.So far,only data about CTLA-4Ig in treating rheumatoid arthritis are available.These data showed that CTLA-4Ig could relieve the symptoms of rheumatoid arthritis and retard the development of the disease.It is safe and effective.In addition,effectiveness was demonstrated even in patients who failed to response to anti-TNF monoclonal antibodies.Therefore,CTLA-4Ig is an encouraging therapy for rheumatic diseases.However,because of very short history,long-term study is needed to fully understand its role in the treatment of rheumatoid arthritis.