狼疮针对B细胞治疗的最新进展

        系统性红斑狼疮是一种以免疫系统大量异常为特点的典型自身免疫病。其免疫异常最可能源自病理性自身抗体产生、免疫复合物沉积和随后的脏器损害。B细胞在发病机制中发挥了重要作用，因此，针对B细胞的治疗包括减少B细胞和阻抑B细胞存活因子如B淋巴细胞刺激因子（BlyS）均为SLE治疗的潜在靶位。来自20项非对照性临床研究发现，利妥昔（人鼠嵌合型抗CD20单抗）能有效地减少B细胞，降低病情活动，并降低血清自身抗体，在仅400例难治性SLE中的临床疗效达86%（合并或不合并用环磷酰胺）。Epratuzumab是一种人源化抗CD22单抗，能部分降低B细胞，能降低中度活动性SLE的病情活动，但不能降低抗体水平。Belimumab是一种人源化抗BlyS单抗，在针对活动性SLE的随机对照I/II期临床试验显示，它能降低B细胞数，抑制SLE病情活动和降低抗ds-DNA抗体。以上所有的治疗耐受性良好，但观察到了随后的感染合并症。以B细胞为靶位的其他治疗包括针对CD20的人化单抗（如Ocrelizumab）及能干扰T细胞和B淋巴细胞相互作用的制剂也具有潜在作用，它们与以上提到单抗的疗效还需通过随机对照试验来证实。

        附原文：Systemic lupus erythematosus (SLE) is a classic autoimmune disease characterized by a myriad of immune system aberrations, most likely resulting from pathogenic autoantibody production, immune complex deposition, and subsequent end-organ damage. B cells play a key role in the pathogenesis; therefore, B-cell-targeted therapies, including B-cell depletion and blockage of B-cell survival factors such as B-lymphocyte stimulator (BLyS), are potential therapeutic targets for SLE. In uncontrolled clinical trials from approximately 20 studies, rituximab--a mouse-human chimeric anti-CD20 monoclonal antibody that effectively depletes B cells--has been demonstrated to reduce disease activity and decrease serum autoantibodies, with a clinical response of 86% in a case series of approximately 400 SLE patients with refractory disease, with or without concomitant use of cyclophosphamide. Epratuzumab, a humanized anti-CD22 monoclonal antibody that partially depletes B cells, has also been shown to reduce disease activity but not to decrease autoantibody levels in patients with moderately active SLE. Randomized controlled phase I/II trials in patients with active SLE have documented that belimumab, a humanized anti-BLyS monoclonal antibody, reduces B-cell numbers, inhibits disease activity and decreases anti-double-stranded DNA autoantibody in SLE patients. All these therapies are well tolerated, but accompanying infectious complications have been observed. Other B-cell-targeted therapies such as 'humanized' monoclonal antibodies to CD20 (e.g. ocrelizumab) and agents that interrupt B-cell/T-cell interactions also have potential, and the efficacy of these, along with rituximab, belimumab and epratuzumab, needs to be determined by randomized controlled trials.【引自 Ding C, Foote S, Jones G. B-cell-targeted therapy for systemic lupus erythematosus: an update. BioDrugs，2008;22(4):239-49.】

TAG: 进展 狼疮 细胞 治疗