Zhang Yanjia, Li Dong
Tianjin Children's Hospital (Tianjin University Children's Hospital), Tianjin, China.
Department of Medicine, Tianjin University, Tianjin, China.
Front Immunol. 2025 May 20;16:1530977. doi: 10.3389/fimmu.2025.1530977. eCollection 2025.
Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) is a rare acquired demyelinating syndrome manifesting as optic neuritis (ON), transverse myelitis (TM), acute disseminated encephalomyelitis (ADEM), and brainstem encephalitis. The disease is characterized by serum autoantibodies targeting myelin oligodendrocyte glycoprotein (MOG), which is exclusively expressed on central nervous system (CNS) myelin and oligodendrocyte membranes. Experimental autoimmune encephalomyelitis (EAE) models have been instrumental in elucidating how these antibodies trigger complement-dependent cytotoxicity (CDC) and antibody-dependent cellular responses, leading to inflammatory demyelination. With most patients experiencing relapses and approximately 50% developing permanent disabilities, therapeutic strategies focus on reducing relapse frequency and severity. MOG-EAE models have directly informed acute treatment approaches including corticosteroids, plasma exchange (PLEX), and intravenous immunoglobulin (IVIG). Mechanistic studies in MOG-EAE models have revealed complex treatment responses and identified several translational targets, including complement inhibition, B-cell depletion strategies, and cytokine-directed therapies that are now advancing to clinical trials. Current immunosuppressive therapies include azathioprine (AZA), mycophenolate mofetil (MMF), and rituximab (RTX), with their differential efficacy in MOGAD versus MS and AQP4-NMOSD now explained by EAE model findings on distinct immunopathological mechanisms. Guided by EAE translational insights into MOGAD pathophysiology, ongoing clinical trials are evaluating novel targeted therapies including complement inhibitors, plasma cell-depleting agents, and antigen-specific tolerization approaches. These EAE-derived mechanistic insights are critical for developing personalized treatment strategies that address the unique immunopathology of this challenging condition.
髓鞘少突胶质细胞糖蛋白抗体相关疾病（MOGAD）是一种罕见的获得性脱髓鞘综合征，表现为视神经炎（ON）、横贯性脊髓炎（TM）、急性播散性脑脊髓炎（ADEM）和脑干脑炎。该疾病的特征是血清自身抗体靶向髓鞘少突胶质细胞糖蛋白（MOG），MOG仅在中枢神经系统（CNS）的髓鞘和少突胶质细胞膜上表达。实验性自身免疫性脑脊髓炎（EAE）模型有助于阐明这些抗体如何触发补体依赖性细胞毒性（CDC）和抗体依赖性细胞反应，从而导致炎症性脱髓鞘。由于大多数患者会复发，约50%的患者会出现永久性残疾，治疗策略的重点是降低复发频率和严重程度。MOG-EAE模型直接为急性治疗方法提供了依据，包括皮质类固醇、血浆置换（PLEX）和静脉注射免疫球蛋白（IVIG）。MOG-EAE模型的机制研究揭示了复杂的治疗反应，并确定了几个可转化的靶点，包括补体抑制、B细胞耗竭策略和细胞因子导向疗法，这些疗法目前正在推进到临床试验阶段。目前的免疫抑制疗法包括硫唑嘌呤（AZA）、霉酚酸酯（MMF）和利妥昔单抗（RTX），EAE模型关于不同免疫病理机制的研究结果现在解释了它们在MOGAD与MS和AQP4-NMOSD中的不同疗效。在EAE对MOGAD病理生理学的转化见解的指导下，正在进行的临床试验正在评估新型靶向疗法，包括补体抑制剂、浆细胞耗竭剂和抗原特异性耐受方法。这些源自EAE的机制见解对于制定个性化治疗策略至关重要，这些策略可应对这一具有挑战性的疾病的独特免疫病理学。
