Department of Multiple Sclerosis Therapeutics, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai 980-8574, Japan.
J Neurol Sci. 2011 Jul 15;306(1-2):183-7. doi: 10.1016/j.jns.2011.02.018. Epub 2011 Mar 11.
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.
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。长期以来，关于 NMO 是否是多发性硬化症（MS）的一种变体或不同疾病存在争议。然而，自从发现水通道蛋白 4（AQP4）的 NMO 特异性自身抗体以来，AQP4 是中枢神经系统中表达丰富的主要水通道，在星形胶质细胞足突上表达，NMO 和 MS 之间的临床区别变得清晰，现在 AQP4 抗体状态对神经科医生决定治疗策略至关重要。此外，病理研究表明，在急性 NMO 病变中，AQP4 和神经胶质纤维酸性蛋白（GFAP）的免疫反应性广泛丧失，而在 MS 中则没有。事实上，在 NMO 急性恶化期间，脑脊液中的 GFAP 水平显著升高，而 MS 中的值与对照组没有差异。此外，最近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、治疗和发病机制意义，并且 AQP4 抗体介导的严重星形胶质细胞损伤将 NMO 与 MS 区分开来。
