Roemer Shanu F, Parisi Joseph E, Lennon Vanda A, Benarroch Eduardo E, Lassmann Hans, Bruck Wolfgang, Mandler Raul N, Weinshenker Brian G, Pittock Sean J, Wingerchuk Dean M, Lucchinetti Claudia F
Department of Neurology, Mayo Clinic, College of Medicine, 200 First St. SW, Rochester, MN 55905, USA.
Brain. 2007 May;130(Pt 5):1194-205. doi: 10.1093/brain/awl371. Epub 2007 Feb 4.
Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that typically affects optic nerves and spinal cord. Its pathogenic relationship to multiple sclerosis (MS) is uncertain. Unlike MS, NMO lesions are characterized by deposits of IgG and IgM co-localizing with products of complement activation in a vasculocentric pattern around thickened hyalinized blood vessels, suggesting a pathogenic role for humoral immunity targeting an antigen in the perivascular space. A recently identified specific serum autoantibody biomarker, NMO-IgG, targets aquaporin-4 (AQP4), the most abundant water channel protein in the CNS, which is highly concentrated in astrocytic foot processes. We analysed and compared patterns of AQP4 immunoreactivity in CNS tissues of nine patients with NMO, 13 with MS, nine with infarcts and five normal controls. In normal brain, optic nerve and spinal cord, the distribution of AQP4 expression resembles the vasculocentric pattern of immune complex deposition observed in NMO lesions. In contrast to MS lesions, which exhibit stage-dependent loss of AQP4, all NMO lesions demonstrate a striking loss of AQP4 regardless of the stage of demyelinating activity, extent of tissue necrosis, or site of CNS involvement. We identified a novel NMO lesion in the spinal cord and medullary tegmentum extending into the area postrema, characterized by AQP4 loss in foci that were inflammatory and oedematous, but neither demyelinated nor necrotic. Foci of AQP4 loss coincided with sites of intense vasculocentric immune complex deposition. These findings strongly support a role for a complement activating AQP4-specific autoantibody as the initiator of the NMO lesion, and further distinguish NMO from MS.
视神经脊髓炎（NMO）是一种炎症性脱髓鞘疾病，通常累及视神经和脊髓。其与多发性硬化症（MS）的致病关系尚不确定。与MS不同，NMO病变的特征是IgG和IgM沉积，与补体激活产物共定位，呈血管中心模式，围绕增厚的玻璃样变血管，提示针对血管周围间隙抗原的体液免疫具有致病作用。最近鉴定出的一种特异性血清自身抗体生物标志物NMO-IgG，靶向水通道蛋白4（AQP4），这是中枢神经系统中最丰富的水通道蛋白，高度集中在星形胶质细胞足突中。我们分析并比较了9例NMO患者、13例MS患者、9例梗死患者和5例正常对照者的中枢神经系统组织中AQP4免疫反应模式。在正常脑、视神经和脊髓中，AQP4表达的分布类似于在NMO病变中观察到的免疫复合物沉积的血管中心模式。与表现出AQP4阶段性丧失的MS病变不同，所有NMO病变均表现出AQP4显著丧失，无论脱髓鞘活动阶段、组织坏死程度或中枢神经系统受累部位如何。我们在脊髓和延髓被盖中发现了一个新的NMO病变，延伸至最后区，其特征是病灶中AQP4丧失，这些病灶有炎症和水肿，但既无脱髓鞘也无坏死。AQP4丧失的病灶与强烈的血管中心免疫复合物沉积部位一致。这些发现有力地支持了补体激活的AQP4特异性自身抗体作为NMO病变起始因素的作用，并进一步将NMO与MS区分开来。
