B淋巴细胞活化因子抗体在自身免疫性疾病治疗中的研究进展

Advances of using antibody against B cell activating factor for treatment of autoimmune diseases

摘要:

近几十年来，自身免疫性疾病的治疗已从使用激素和常规免疫抑制药物转向使用生物制剂。B淋巴细胞的增殖及成熟对自身免疫性疾病的发病起到至关重要的作用。其中，肿瘤坏死因子超家族B淋巴细胞活化因子(B cell activating factor，BAFF)及其受体通过调控信号通路介导B淋巴细胞存活，因此BAFF及其受体是自身免疫性疾病的重要治疗靶点。文中阐述了BAFF及其受体在人体免疫系统中的作用机制，同时介绍了BAFF通路的过度活化如何促进系统性红斑狼疮、干燥综合征和类风湿关节炎等自身免疫疾病发展的最新观点。针对以上3种疾病，文中以3种主要的靶向BAFF抗体药物Belimumab、Tabalumab和Atacicept为例，介绍和讨论了其最新的临床试验及临床应用现状。最后提出靶向BAFF通路开发新型治疗自身免疫性疾病的方案和策略。

Abstract:

In recent decades,the treatment of autoimmune diseases has moved from the use of hormones and conventional immunosuppressive drugs to biological agents.B cell proliferation and maturation play crucial roles in the development of autoimmune diseases.The tumor necrosis factor superfamily ligand B cell activating factor (BAFF) and its receptor mediate B cell survival through regulating signaling pathways.Therefore,BAFF and its receptors are important therapeutic targets for the treatment of autoimmune diseases.This review describes the mechanism of BAFF and its receptor in the human body system and introduces the latest views on how over-activation of BAFF pathway promotes the development of autoimmune diseases including systemic lupus erythematosus,Sjogren’s syndrome,and rheumatoid arthritis.In connection to the treatment of the above three diseases,this review discusses the clinical trials and application status of three BAFF-targeting antibody drugs,including Belimumab,Tabalumab and Atacicept.Finally,this review proposes new strategies that targeting the BAFF pathway to provide a new treatment for autoimmune diseases.