Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disease affecting the central nervous system (CNS), often characterized by the accumulation of irreversible clinical disability over time. During last years, there has been a dramatic evolution in several key concepts of immune pathophysiology of MS and in the treatment of this disease. The demonstration of the strong efficacy and good safety profile of selective B-cell-depleting therapies (such as anti-CD20 monoclonal antibodies) has significantly expanded the therapeutic scenario for both relapsing and progressive MS patients with the identification of a new therapeutic target. The key role of B cells in triggering MS disease has been also pointed out, determining a shift from the traditional view of MS activity as largely being 'T-cell mediated' to the notion that MS-related pathological processes involve bi-directional interactions between several immune cell types, including B cells, both in the periphery and in the CNS. This review provides an updated overview of the involvement of B cells in the immune pathophysiology and pathology of MS. We summarize the rationale regarding the use of anti-CD20 therapies and the results of the main randomized controlled trials and observational studies investigating the efficacy and safety profile of rituximab, ocrelizumab, ofatumumab and ublituximab. Suggestions regarding vaccinations and management of MS patients during COVID-19 pandemic with anti-CD20 therapies are also discussed. Finally, therapies under investigation and future perspectives of anti-CD20 therapies are taken into consideration.

中文翻译：

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多发性硬化症的抗 CD20 疗法：现状和未来展望。

多发性硬化症 (MS) 是一种影响中枢神经系统 (CNS) 的慢性炎症、脱髓鞘和神经退行性疾病，其特征通常是随着时间的推移累积不可逆的临床残疾。在过去几年中，MS 免疫病理生理学的几个关键概念和该疾病的治疗发生了巨大的变化。选择性 B 细胞消耗疗法（如抗 CD20 单克隆抗体）的强大功效和良好安全性的证明显着扩大了复发和进展 MS 患者的治疗方案，并确定了新的治疗靶点。还指出了 B 细胞在引发 MS 疾病中的关键作用，确定了从传统观点的转变，即 MS 活动主要是“T 细胞介导的” 认为 MS 相关的病理过程涉及几种免疫细胞类型之间的双向相互作用，包括外周和中枢神经系统中的 B 细胞。本综述提供了 B 细胞参与 MS 的免疫病理生理学和病理学的最新概述。我们总结了使用抗 CD20 疗法的基本原理以及主要的随机对照试验和观察性研究的结果，调查了利妥昔单抗、ocrelizumab、ofatumumab 和 ublituximab 的疗效和安全性。还讨论了在 COVID-19 大流行期间使用抗 CD20 疗法对 MS 患者进行疫苗接种和管理的建议。最后，考虑了正在研究的疗法和抗 CD20 疗法的未来前景。