Conformation-sensitive antibodies against myelin oligodendrocyte glycoprotein (MOG) are detectable in patients with optic neuritis, myelitis, opticomyelitis, acute or multiphasic disseminated encephalomyelitis (ADEM/MDEM) and brainstem/cerebral cortical encephalitis, but are rarely detected in patients with prototypic multiple sclerosis. So far, there has been no systematic study on the pathological relationship between demyelinating lesions and cellular/humoral immunity in MOG antibody-associated disease. Furthermore, it is unclear whether the pathomechanisms of MOG antibody-mediated demyelination are similar to the demyelination patterns of multiple sclerosis, neuromyelitis optica spectrum disorders (NMOSD) with AQP4 antibody, or ADEM. In this study, we immunohistochemically analysed biopsied brain tissues from 11 patients with MOG antibody-associated disease and other inflammatory demyelinating diseases. Patient median onset age was 29 years (range 9-64), and the median interval from attack to biopsy was 1 month (range 0.5-96). The clinical diagnoses were ADEM (n = 2), MDEM (n = 1), multiple brain lesions without encephalopathy (n = 3), leukoencephalopathy (n = 3) and cortical encephalitis (n = 2). All these cases had multiple/extensive lesions on MRI and were oligoclonal IgG band-negative. Most demyelinating lesions in 10 of 11 cases showed a perivenous demyelinating pattern previously reported in ADEM (153/167 lesions) and a fusion pattern (11/167 lesions) mainly in the cortico-medullary junctions and white matter, and only three lesions in two cases showed confluent demyelinated plaques. In addition, 60 of 167 demyelinating lesions (mainly in the early phase) showed MOG-dominant myelin loss, but relatively preserved oligodendrocytes, which were distinct from those of AQP4 antibody-positive NMOSD exhibiting myelin-associated glycoprotein-dominant oligodendrogliopathy. In MOG antibody-associated diseases, MOG-laden macrophages were found in the perivascular spaces and demyelinating lesions, and infiltrated cells were abundant surrounding multiple blood vessels in and around the demyelinating lesions, mainly consisting of macrophages (CD68; 1814 ± 1188 cells/mm2), B cells (CD20; 468 ± 817 cells/mm2), and T cells (CD3; 2286 ± 1951 cells/mm2), with CD4-dominance (CD4+ versus CD8+; 1281 ± 1196 cells/mm2 versus 851 ± 762 cells/mm2, P < 0.01). Humoral immunity, evidenced by perivascular deposits of activated complements and immunoglobulins, was occasionally observed in some MOG antibody-associated demyelinating lesions, and the frequency was much lower than that in AQP4 antibody-positive NMOSD. Subpial lesions with perivenous demyelination were observed in both ADEM and cortical encephalitis. Our study suggests that ADEM-like perivenous inflammatory demyelination with MOG-dominant myelin loss is a characteristic finding of MOG antibody-associated disease regardless of whether the diagnostic criteria of ADEM are met. These pathological features are clearly different from those of multiple sclerosis and AQP4 antibody-positive NMOSD, suggesting an independent autoimmune demyelinating disease entity.

中文翻译：

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髓磷脂少突胶质细胞糖蛋白抗体相关疾病：一项免疫病理研究。

在视神经炎，脊髓炎，视神经脊髓炎，急性或多相弥漫性脑脊髓炎（ADEM / MDEM）和脑干/脑皮质脑炎患者中可检测到针对髓鞘少突胶质细胞糖蛋白（MOG）的构象敏感抗体，但在原型多发性硬化症患者中很少发现。迄今为止，尚未有关于MOG抗体相关疾病中脱髓鞘性病变与细胞/体液免疫之间的病理关系的系统研究。此外，还不清楚MOG抗体介导的脱髓鞘的发病机制是否与多发性硬化症，AQP4抗体引起的视神经脊髓炎光谱障碍（NMOSD）或ADEM的脱髓鞘模式相似。在这个研究中，我们对11例MOG抗体相关疾病和其他炎症性脱髓鞘疾病患者的活检组织进行了免疫组织化学分析。患者中位发病年龄为29岁（范围9-64），从发作到活检的中位间隔为1个月（范围0.5-96）。临床诊断为ADEM（n = 2），MDEM（n = 1），无脑病的多发性脑病（n = 3），白质脑病（n = 3）和皮质性脑炎（n = 2）。所有这些病例在MRI上均具有多发性/广泛性病变，并且寡克隆IgG带阴性。11例中有10例的大多数脱髓鞘病变均表现出ADEM先前报道的静脉脱髓鞘样变（153/167病变）和融合模式（11/167病变），主要出现在皮质-髓质交界处和白质，只有两个病变中有三个病例显示融合的脱髓鞘斑块。此外，在167个脱髓鞘病变中，有60个（主要在早期阶段）表现出MOG为主的髓鞘丧失，但相对保存的少突胶质细胞，与表现出髓鞘相关的糖蛋白为主的少突胶质病的AQP4抗体阳性的NMOSD明显不同。在与MOG抗体相关的疾病中，在血管周间隙和脱髓鞘病变中发现了载有MOG的巨噬细胞，在脱髓鞘病变中和周围的多处血管周围浸润的细胞丰富，主要由巨噬细胞组成（CD68; 1814±1188细胞/ mm2 ），B细胞（CD20; 468±817细胞/ mm2）和T细胞（CD3; 2286±1951细胞/ mm2），具有CD4优势（CD4 +与CD8 +; 1281±1196细胞/ mm2与851±762细胞/ mm2，P <0.01）。体液免疫力 在一些MOG抗体相关的脱髓鞘病变中偶尔观察到活化的补体和免疫球蛋白在血管周围沉积的证据，其发生频率远低于AQP4抗体阳性的NMOSD。在ADEM和皮质脑炎中均观察到伴有静脉脱髓鞘的皮下病变。我们的研究表明，无论是否符合ADEM的诊断标准，伴有MOG显性髓磷脂丢失的ADEM样静脉炎性脱髓鞘是MOG抗体相关疾病的特征性发现。这些病理特征与多发性硬化症和AQP4抗体阳性的NMOSD明显不同，表明存在独立的自身免疫性脱髓鞘疾病实体。而且频率远低于AQP4抗体阳性的NMOSD。在ADEM和皮质脑炎中均观察到伴有静脉脱髓鞘的皮下病变。我们的研究表明，无论是否符合ADEM的诊断标准，伴有MOG显性髓磷脂丢失的ADEM样静脉炎性脱髓鞘是MOG抗体相关疾病的特征性发现。这些病理特征与多发性硬化症和AQP4抗体阳性的NMOSD明显不同，表明存在独立的自身免疫性脱髓鞘疾病实体。而且频率远低于AQP4抗体阳性的NMOSD。在ADEM和皮层脑炎中均观察到伴有静脉脱髓鞘的皮下病变。我们的研究表明，无论是否符合ADEM的诊断标准，伴有MOG显性髓磷脂丢失的ADEM样静脉炎性脱髓鞘是MOG抗体相关疾病的特征性发现。这些病理特征与多发性硬化症和AQP4抗体阳性的NMOSD明显不同，表明存在独立的自身免疫性脱髓鞘疾病实体。我们的研究表明，无论是否符合ADEM的诊断标准，伴有MOG显性髓磷脂丢失的ADEM样静脉炎性脱髓鞘是MOG抗体相关疾病的特征性发现。这些病理特征与多发性硬化症和AQP4抗体阳性的NMOSD明显不同，表明存在独立的自身免疫性脱髓鞘疾病实体。我们的研究表明，无论是否符合ADEM的诊断标准，伴有MOG显性髓磷脂丢失的ADEM样静脉炎性脱髓鞘是MOG抗体相关疾病的特征性发现。这些病理特征与多发性硬化症和AQP4抗体阳性的NMOSD明显不同，表明存在独立的自身免疫性脱髓鞘疾病实体。