靶向B细胞治疗系统性红斑狼疮研究进展

ADVANCES IN TARGETED B-CELL THERAPY FOR SYSTEMIC LUPUS ERYTHEMATOSUS

系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种慢性、全身多系统受累的自身免疫性疾病,其病因和发病机制尚未完全明确。作为适应性免疫应答的主要组成部分,B细胞在自身免疫性疾病中起到了关键作用。已有研究表明,自身反应性B细胞过度增殖、活化,从而产生多种自身抗体是SLE发病至关重要的环节,也是造成全身多脏器损害的病理基础[1]。靶向B细胞治疗可抑制B细胞的活化、增殖,减少自身抗体的产生,因此B细胞在近些年成为了SLE治疗的新型靶点。国内外亦进行了多项临床研究证实了B细胞靶向治疗药物的有效性及安全性,如贝利尤单抗、利妥昔单抗、泰它西普等,为SLE治疗的进展提供了更多证据。本综述主要围绕靶向B细胞治疗的进展进行讨论,包括靶向B细胞表面抗原、靶向B细胞因子、共刺激阻断、酪氨酸蛋白激酶抑制剂等。

Systemic lupus erythematosus(SLE)is a chronic,systemic,multi-systemic autoimmune disease whose eti-ology and pathogenesis are not fully understood.As a major component of the adaptive immune response,B cells play a key role in autoimmune disease.It has been shown that the overproliferation and activation of auto-reactive B cells,resulting in the production of multiple auto-antibodies,is a critical component in the pathogenesis of SLE and is the pathological basis for the damage to multiple organs throughout the body.Targeted B-cell therapy can inhibit the activation and proliferation of B-cells and reduce the production of auto-antibodies,therefore B-cells have become a new target for SLE treatment in recent years.This review will focus on advances in targeted B-cell therapy,including targeting B-cell surface antigens,targeting B-cell factors,co-stimulatory blockade,tyrosine protein kinase inhibitors,etc.