Department of Neurology, Barzilai University Medical Center, Ashkelon, Israel; Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Autoimmun Rev. 2016 Jul;15(7):714-8. doi: 10.1016/j.autrev.2016.03.006. Epub 2016 Mar 9.
Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system (CNS) that traditionally has been considered to be mediated primarily by T-cells. Increasing evidence, however, suggests the fundamental role of B-cells in the pathogenesis of the disease. Recent strategies targeting B-cells in MS have demonstrated impressive and sometimes surprising results: B-cell depletion by monoclonal antibodies targeting the B-cell surface antigen CD20 (e.g. rituximab, ocrelizumab, ofatumumab) was shown to exert profound anti-inflammatory effect in MS with favorable risk-benefit ratio, with ocrelizumab demonstrating efficacy in both relapsing-remitting (RR) and primary-progressive (PP) MS in phase III clinical trials. Depletion of CD52 expressing T- and B-cells and monocytes by alemtuzumab resulted in impressive and durable suppression of disease activity in RRMS patients. On the other hand, strategies targeting B-cell cytokines such as atacicept resulted in increased disease activity. As our understanding of the biology of B-cells in MS is increasing, new compounds that target B-cells continue to be developed which promise to further expand the armamentarium of MS therapies and allow for more individualized therapy for patients with this complex disease.
多发性硬化症（MS）是一种中枢神经系统（CNS）的慢性炎症性脱髓鞘疾病，传统上被认为主要由 T 细胞介导。然而，越来越多的证据表明 B 细胞在疾病发病机制中的基本作用。最近针对 MS 中 B 细胞的策略已经证明了令人印象深刻的，有时甚至是令人惊讶的结果：针对 B 细胞表面抗原 CD20 的单克隆抗体（如利妥昔单抗、奥瑞珠单抗、奥法妥珠单抗）可通过 B 细胞耗竭在 MS 中发挥深远的抗炎作用，具有良好的风险效益比，奥瑞珠单抗在 III 期临床试验中显示出对 RRMS 和原发性进展性 MS（PPMS）的疗效。阿仑单抗可耗竭表达 CD52 的 T 细胞、B 细胞和单核细胞，导致 RRMS 患者的疾病活动显著且持久地抑制。另一方面，针对 B 细胞细胞因子（如阿他西普）的策略导致疾病活动增加。随着我们对 MS 中 B 细胞生物学的理解不断增加，继续开发针对 B 细胞的新化合物有望进一步扩大 MS 治疗的武器库，并为患有这种复杂疾病的患者提供更个体化的治疗。
