Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
J Neurol Sci. 2011 Dec 15;311(1-2):69-77. doi: 10.1016/j.jns.2011.08.043. Epub 2011 Sep 29.
Neuromyelitis optica (NMO) selectively affects the optic nerves and spinal cord. In Asians, multiple sclerosis (MS) is rare; however, when it appears, the selective and severe involvement of the optic nerves and spinal cord is characteristic. This form, termed opticospinal multiple sclerosis (OSMS), has similar features to the relapsing form of NMO in Westerners. The discovery that NMO-IgG, an NMO-specific IgG, targets aquaporin-4 (AQP4), suggested that NMO is a distinct disease entity with a fundamentally different etiology from MS. Because NMO-IgG is present in 30-60% of OSMS patients, OSMS in Asians is suggested to be the same entity as NMO. Pathologically, perivascular immune complex (IgM, IgG and C9neo) deposition and extensive loss of AQP4 in active lesions are reported hallmarks of NMO. However, we found that some autopsied NMO cases showed selective AQP4 loss while others showed preservation of AQP4, despite extensive tissue destruction. Vasculocentric deposition of complement and immunoglobulin was detected only in NMO patients, with less than 30% of actively demyelinating lesions showing AQP4 loss. Such heterogeneity of AQP4 expression and immunoglobulin deposition suggests a heterogeneous disease process in NMO. We recently reported that AQP4 was extensively lost in glial fibrillary acidic protein-positive hypertrophic astrocytes, both in demyelinated and myelinated layers of actively demyelinating lesions in Baló's disease, a variant of MS. We also found that in some acute MS lesions, AQP4 was lost extensively far beyond the areas of myelin loss. Active demyelinating lesions involved perivascular lymphocyte cuffings, consisting mainly of T cells in Baló's disease and MS, while the same was true for approximately half of the active lesions in NMO. This review proposes that anti-AQP4 antibody-dependent AQP4 loss occurs in some NMO patients while antibody-independent AQP4 astrocytopathy can occur in heterogeneous demyelinating conditions, including Baló's disease, NMO and MS. The latter may be mediated by T cells and other cell-mediated mechanisms, and should be tested in future experimental studies.
视神经脊髓炎（NMO）选择性地影响视神经和脊髓。在亚洲人中，多发性硬化症（MS）很少见；然而，当它出现时，视神经和脊髓的选择性和严重受累是其特征。这种形式被称为视神经脊髓多发性硬化症（OSMS），与西方人复发性 NMO 具有相似的特征。发现 NMO 特异性 IgG（NMO-IgG）靶向水通道蛋白-4（AQP4），提示 NMO 是一种与 MS 具有根本不同病因的独特疾病实体。由于 NMO-IgG 存在于 30-60%的 OSMS 患者中，因此亚洲的 OSMS 被认为与 NMO 是同一实体。在病理学上，报道了血管周围免疫复合物（IgM、IgG 和 C9neo）沉积和活跃病变中广泛的 AQP4 丢失是 NMO 的标志。然而，我们发现一些尸检 NMO 病例表现出选择性 AQP4 丢失，而另一些则表现出 AQP4 保留，尽管组织破坏广泛。补体和免疫球蛋白的血管中心沉积仅在 NMO 患者中检测到，不到 30%的活跃脱髓鞘病变显示 AQP4 丢失。AQP4 表达和免疫球蛋白沉积的这种异质性提示 NMO 中存在异质性疾病过程。我们最近报道称，在 Baló 病（MS 的一种变体）中，活跃脱髓鞘病变的脱髓鞘和髓鞘层中，胶质纤维酸性蛋白阳性肥大星形胶质细胞中广泛丢失 AQP4。我们还发现，在一些急性 MS 病变中，AQP4 远远超出髓鞘丢失区域广泛丢失。活跃的脱髓鞘病变涉及血管周围淋巴细胞袖套，在 Baló 病和 MS 中主要由 T 细胞组成，而在 NMO 的大约一半活跃病变中也是如此。本综述提出，在一些 NMO 患者中发生抗 AQP4 抗体依赖性 AQP4 丢失，而在包括 Baló 病、NMO 和 MS 在内的异质性脱髓鞘疾病中，可能发生抗体非依赖性 AQP4 星形胶质细胞病。后者可能由 T 细胞和其他细胞介导机制介导，应在未来的实验研究中进行测试。
