Loss of aquaporin 4 in lesions of neuromyelitis optica: distinction from multiple sclerosis
Loss of aquaporin 4 in lesions of neuromyelitis optica: distinction from multiple sclerosis
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DOI：
10.1093/brain/awm047
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发表时间：
2007-05-01
期刊：
影响因子：
14.5
通讯作者：
Itoyama, Y.
中科院分区：
文献类型：
--
作者：
Misu, T.;Fujihara, K.;Itoyama, Y.
视神经肌萎缩症（NMO）是一种以视神经和脊髓选择性受累为特征的炎性和坏死性疾病。关于NMO是多发性硬化症（MS）的一种变体还是一种独特的疾病，一直存在争议。近年来，在NMO患者血清中发现了一种NMO特异性抗体（NMO-IgG），其靶抗原被鉴定为水通道蛋白4（AQP 4），主要表达于星形胶质细胞足突。然而，AQP 4在NMO中的致病作用仍不清楚。对12例NMO、B期MS、7例脑梗死和8例正常对照组的脊髓病变和延髓组织进行了AQP 4、胶质细胞酸性蛋白（GFAP）、髓鞘碱性蛋白（MBP）、活化补体C9 neo和免疫球蛋白的免疫组织化学研究。最引人注目的发现是，AQP 4免疫反应性在总共67个急性和慢性NMO病变中的60个（90%）中丢失，但在MS斑块中没有丢失。AQP 4的广泛丢失伴随着GFAP染色的减少是明显的，特别是在活动性血管周围病变中，免疫球蛋白和活化的补体沉积。有趣的是，在这些NMO病变中，尽管AQP 4和GFAP染色丧失，但MBP染色的有髓纤维相对保留。在NMO中，病变周围区域AQP 4和GFAP表达增强，反映了反应性胶质增生。与此相反，AQP 4免疫反应性保存良好，而强烈的染色在脱髓鞘MS斑块，和梗死也染色的AQP 4从非常急性阶段的坏死到慢性阶段的星形胶质细胞增生。在正常对照组中，AQP 4在整个组织切片中弥漫表达，但在脊髓中的染色在中央灰质中比在白色物质中更强。本研究表明，AQP 4和GFAP的免疫反应性一致失去了从早期阶段的损害在NMO，特别是在血管周围的区域与补体和免疫球蛋白沉积。NMO的这些特征与MS和梗死以及正常对照的特征不同，并且表明与AQP 4和体液免疫的丧失相关的星形胶质细胞损伤在NMO病变的发病机制中可能是重要的。
Neuromyelitis optica (NMO) is an inflammatory and necrotizing disease clinically characterized by selective involvement of the optic nerves and spinal cord. There has been a long controversy as to whether NMO is a variant of multiple sclerosis (MS) or a distinct disease. Recently, an NMO-specific antibody (NMO-IgG) was found in the sera from patients with NMO, and its target antigen was identified as aquaporin 4 (AQP4) water channel protein, mainly expressed in astroglial foot processes. However, the pathogenetic role of the AQP4 in NMO remains unknown. We did an immunohistopathological study on the distribution of AQP4, glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), activated complement C9neo and immunoglobulins in the spinal cord lesions and medulla oblongata of NMO (n = 12), MS (n = b), brain and spinal infarction (n = 7) and normal control (n = 8). The most striking finding was that AQP4 immunoreactivity was lost in 60 out of a total of 67 acute and chronic NMO lesions (90%), but not in MS plaques. The extensive loss of AQP4 accompanied by decreased GFAP staining was evident, especially in the active perivascular lesions, where immunoglobulins and activated complements were deposited. Interestingly, in those NMO lesions, MBP-stained myelinated fibres were relatively preserved despite the loss of AQP4 and GFAP staining. The areas surrounding the lesions in NMO had enhanced expression of AQP4 and GFAP, which reflected reactive gliosis. In contrast, AQP4 immunoreactivity was well preserved and rather strongly stained in the demyelinating MS plaques, and infarcts were also stained for AQP4 from the very acute phase of necrosis to the chronic stage of astrogliosis. In normal controls, AQP4 was diffusely expressed in the entire tissue sections, but the staining in the spinal cord was stronger in the central grey matter than in the white matter. The present study demonstrated that the immunoreactivities of AQP4 and GFAP were consistently lost from the early stage of the lesions in NMO, notably in the perivascular regions with complement and immunoglobulin deposition. These features in NMO were distinct from those of MS and infarction as well as normal controls, and suggest that astrocytic impairment associated with the loss of AQP4 and humoral immunity may be important in the pathogenesis of NMO lesions.