Neuromyelitis optica and astrocytic damage in its pathogenesis
Neuromyelitis optica and astrocytic damage in its pathogenesis
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DOI：
10.1016/j.jns.2011.02.018
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发表时间：
2011-07-15
影响因子：
4.4
通讯作者：
Fujihara, Kazuo
中科院分区：
文献类型：
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作者：
Fujihara, Kazuo
视神经脊髓炎(NMO)的特征是严重的视神经炎和纵向延伸的横贯性脊髓炎。NMO是多发性硬化症(MS)的变种还是另一种疾病，长期以来一直存在争议。然而，自从发现了NMO特异性的抗水通道蛋白4(AQP4)的自身抗体以来，NMO和MS之间的临床区别变得清晰起来，现在AQP4抗体的状态对神经科医生决定治疗策略至关重要。AQP4是中枢神经系统中主要的水通道，密集表达在星形胶质细胞的足突上。此外，病理研究表明，急性NMO皮损中AQP4和胶质纤维酸性蛋白(GFAP)的免疫反应活性广泛丧失，髓鞘碱性蛋白的染色相对保留，这在MS中是看不到的。事实上，NMO急性加重期脑脊液中GFAP水平显著升高，而MS患者的脑脊液GFAP水平与正常对照组无明显差异。此外，最近进行的体外和体内实验研究表明，AQP4抗体具有致病性。这些发现强烈表明AQP4抗体具有诊断、治疗和病理意义，AQP4抗体介导的严重星形细胞损伤是NMO与MS(C)2011 Elsevier B.V.的区别。保留所有权利。
Neuromyelitis optica (NMO) is characterized by severe optic neuritis and longitudinally extended, transverse myelitis. There have been long controversial whether NMO is a variant of multiple sclerosis (MS) or a different disease. However, since the discovery of an NMO-specific autoantibody to aquaporin 4 (AQP4), a dominant water channel in the central nervous system densely expressed on foot processes of astrocytes, the clinical distinction between NMO and MS has become clear, and now AQP4 antibody status is critically important for neurologists in deciding on treatment strategy. Moreover, pathological studies demonstrated an extensive loss of immunoreactivities to AQP4 and glial fibrillary acidic protein (GFAP) with relative preservation of the staining of myelin basic protein in acute NMO lesions, which is not seen in MS. In fact, the GFAP levels in the cerebrospinal fluid during acute exacerbation of NMO are remarkably elevated, while the values in MS are not different from those in controls. In addition, recent experimental studies conducted in vitro and in vivo have shown that AQP4 antibody is pathogenic. These findings strongly suggest that AQP4 antibody has diagnostic, therapeutic and pathogenetic implications, and that severe astrocytic damage mediated by AQP4 antibody distinguishes NMO from MS. (C) 2011 Elsevier B.V. All rights reserved.