Multiple Sclerosis Center, Department of Neurology, University of California, San Francisco, California 94158.
Cold Spring Harb Perspect Med. 2019 Feb 1;9(2):a032037. doi: 10.1101/cshperspect.a032037.
B cells play a vital function in multiple sclerosis (MS) pathogenesis through an array of effector functions. All currently approved MS disease-modifying therapies alter the frequency, phenotype, or homing of B cells in one way or another. The importance of this mechanism of action has been reinforced with the successful development and clinical testing of B-cell-depleting monoclonal antibodies that target the CD20 surface antigen. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, was approved by the Food and Drug Administration (FDA) in March 2017 after pivotal trials showed dramatic reductions in inflammatory disease activity in relapsing MS as well as lessening of disability progression in primary progressive MS. These and other clinical studies place B cells at the center of the inflammatory cascade in MS and provide a launching point for development of therapies that target selective pathogenic B-cell populations.
B 细胞通过多种效应功能在多发性硬化症 (MS) 的发病机制中发挥着至关重要的作用。目前所有批准的 MS 疾病修正治疗药物都以这样或那样的方式改变 B 细胞的频率、表型或归巢。随着针对 CD20 表面抗原的 B 细胞耗竭单克隆抗体的成功开发和临床测试，这种作用机制的重要性得到了加强。奥瑞珠单抗是一种人源化抗 CD20 单克隆抗体，在关键性试验显示其在复发型 MS 中显著降低炎症性疾病活动度以及在原发性进展型 MS 中减轻残疾进展之后，于 2017 年 3 月获得美国食品和药物管理局 (FDA) 的批准。这些和其他临床研究将 B 细胞置于 MS 炎症级联反应的中心，并为开发针对选择性致病性 B 细胞群体的治疗方法提供了一个起点。
