Institute of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
Department of Neurology, Rigshospitalet, Glostrup, Denmark.
Front Immunol. 2020 Dec 17;11:587078. doi: 10.3389/fimmu.2020.587078. eCollection 2020.
Multiple sclerosis (MS) is a neurologic disease affecting myelinated nerves in the central nervous system (CNS). The disease often debuts as a clinically isolated syndrome, e.g., optic neuritis (ON), which later develops into relapsing-remitting (RR) MS, with temporal attacks or primary progressive (PP) MS. Characteristic features of MS are inflammatory foci in the CNS and intrathecal synthesis of immunoglobulins (Igs), measured as an IgG index, oligoclonal bands (OCBs), or specific antibody indexes. Major predisposing factors for MS are certain tissue types (e.g., HLA DRB1*15:01), vitamin D deficiency, smoking, obesity, and infection with Epstein-Barr virus (EBV). Many of the clinical signs of MS described above can be explained by chronic/recurrent EBV infection and current models of EBV involvement suggest that RRMS may be caused by repeated entry of EBV-transformed B cells to the CNS in connection with attacks, while PPMS may be caused by more chronic activity of EBV-transformed B cells in the CNS. In line with the model of EBV's role in MS, new treatments based on monoclonal antibodies (MAbs) targeting B cells have shown good efficacy in clinical trials both for RRMS and PPMS, while MAbs inhibiting B cell mobilization and entry to the CNS have shown efficacy in RRMS. Thus, these agents, which are now first line therapy in many patients, may be hypothesized to function by counteracting a chronic EBV infection.
多发性硬化症(MS)是一种影响中枢神经系统(CNS)髓鞘神经的神经系统疾病。这种疾病通常以临床孤立综合征(如视神经炎[ON])为首发症状,随后发展为复发缓解型(RR)MS,伴有暂时发作或原发性进展型(PP)MS。MS 的特征性表现为 CNS 中的炎症灶和鞘内免疫球蛋白(Igs)的合成,以 IgG 指数、寡克隆带(OCBs)或特定抗体指数来衡量。MS 的主要易感因素包括某些组织类型(例如 HLA DRB1*15:01)、维生素 D 缺乏、吸烟、肥胖和 Epstein-Barr 病毒(EBV)感染。上述 MS 的许多临床症状可以用慢性/复发性 EBV 感染来解释,目前 EBV 参与的模型表明 RRMS 可能是由于 EBV 转化的 B 细胞在攻击时反复进入中枢神经系统引起的,而 PPMS 可能是由中枢神经系统中 EBV 转化的 B 细胞的更慢性活动引起的。与 EBV 在 MS 中的作用模型一致,基于针对 B 细胞的单克隆抗体(MAb)的新治疗方法在 RRMS 和 PPMS 的临床试验中均显示出良好的疗效,而抑制 B 细胞动员和进入中枢神经系统的 MAb 在 RRMS 中也显示出疗效。因此,这些药物现已成为许多患者的一线治疗药物,它们可能通过抑制慢性 EBV 感染发挥作用。