Menge T, Büdingen H-C, Dalakas M C, Kieseier B C, Hartung H-P
Neurologische Klinik, Heinrich-Heine-Universität, Moorenstrasse 5, 40225, Düsseldorf, Deutschland.
Nervenarzt. 2009 Feb;80(2):190-8. doi: 10.1007/s00115-008-2664-2.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating autoimmune disease of the CNS and a leading cause of lasting neurological disability in younger adults. In the last decade our knowledge of its immunopathogenesis expanded vastly. It is now widely appreciated that B cells are key players in the autoreactive immune network. They exert far more functions than merely being the precursors of antibody-producing plasma cells. B cells act as efficient antigen-presenting cells and may stimulate an autoreactive immune response through secretion of proinflammatory cytokines. It is thus only logical to test therapeutic strategies targeting B cells in MS. Rituximab is a depleting chimeric monoclonal antibody directed against CD20 and expressed on developing, naïve, and memory B cells but not stem or plasma cells. Several smaller studies have been conducted that led to a placebo controlled, double blind phase II study on efficacy which was reported recently. The results are very promising, meeting not only the primary endpoint of reduction of the surrogate MRI marker of contrast-enhancing lesions but also showing a reduction in clinical relapse rate of patients treated with rituximab. This review discusses the role of autoreactive B cells in the context of MS, analyzes the B-cell-depleting treatment studies reported, and provides information on planned and future B-cell-directed therapeutic strategies in MS.
多发性硬化症(MS)是一种中枢神经系统的慢性炎症性脱髓鞘自身免疫性疾病,也是导致年轻人永久性神经功能残疾的主要原因。在过去十年中,我们对其免疫发病机制的认识有了极大的扩展。现在人们普遍认识到,B细胞是自身反应性免疫网络中的关键参与者。它们发挥的功能远不止仅仅作为产生抗体的浆细胞的前体。B细胞作为高效的抗原呈递细胞,可能通过分泌促炎细胞因子来刺激自身反应性免疫应答。因此,在MS中测试针对B细胞的治疗策略是合乎逻辑的。利妥昔单抗是一种针对CD20的消耗性嵌合单克隆抗体,在发育中的、幼稚的和记忆性B细胞上表达,但不在干细胞或浆细胞上表达。已经进行了几项较小规模的研究,这些研究促成了一项关于疗效的安慰剂对照、双盲II期研究,该研究结果最近已被报道。结果非常有前景,不仅达到了降低增强病灶这一替代MRI标志物的主要终点,而且还显示接受利妥昔单抗治疗的患者临床复发率降低。本综述讨论了自身反应性B细胞在MS背景下的作用,分析了已报道的B细胞清除治疗研究,并提供了有关MS中计划和未来针对B细胞的治疗策略的信息。