Lee Wen Shi, Amengual Olga
Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Immunol Med. 2020 Mar;43(1):16-35. doi: 10.1080/25785826.2019.1698929. Epub 2019 Dec 9.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which affects the majority of organs and systems. Traditional therapies do not lead to complete remission of disease but only relieve symptoms and inflammation. B cells are the most important effector cell types in the pathogenesis of SLE. Therefore, therapies targeting B cells and their related cytokines are a very important milestone for SLE treatment. Several biologics that modulate B cells, either depleting B cells or blocking B cell functions, have been developed and evaluated in clinical trials. Belimumab, a fully humanized monoclonal antibody that specifically binds B cells activating factor (BAFF), was the first of these agents approved for SLE treatment. In this review, we explore the currently available evidence in B cell targeted therapies in SLE including agents that target B cell surface antigens (CD19, CD20, CD22), B cell survival factors (BAFF and a proliferation-inducing ligand, APRIL), cytokines (interleukin-1 and type 1 interferons) and co-stimulatory molecules (CD40 ligand). We highlighted the mechanisms of action and the individual characteristics of these biologics, and present an update on the clinical trials that have evaluated their efficacy and safety. Finally, we describe some of the emerging and promising therapies for SLE treatment.
系统性红斑狼疮（SLE）是一种慢性自身免疫性疾病，可累及大多数器官和系统。传统疗法无法使疾病完全缓解，只能缓解症状和炎症。B细胞是SLE发病机制中最重要的效应细胞类型。因此，针对B细胞及其相关细胞因子的疗法是SLE治疗的一个非常重要的里程碑。几种调节B细胞的生物制剂，无论是消耗B细胞还是阻断B细胞功能，都已开发并在临床试验中进行了评估。贝利尤单抗是一种特异性结合B细胞活化因子（BAFF）的全人源单克隆抗体，是这些药物中首个被批准用于SLE治疗的药物。在本综述中，我们探讨了目前SLE中B细胞靶向治疗的现有证据，包括靶向B细胞表面抗原（CD19、CD20、CD22）、B细胞存活因子（BAFF和增殖诱导配体，APRIL）、细胞因子（白细胞介素-1和1型干扰素）和共刺激分子（CD40配体）的药物。我们强调了这些生物制剂的作用机制和个体特征，并介绍了评估其疗效和安全性的临床试验的最新情况。最后，我们描述了一些SLE治疗中新兴且有前景的疗法。
