Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Biochem Biophys Res Commun. 2010 Mar 26;394(1):205-10. doi: 10.1016/j.bbrc.2010.02.157. Epub 2010 Feb 25.
Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system (CNS). Anti-aquaporin-4 antibody (AQP4-Ab) is a highly specific serum autoantibody that is detected in patients with NMO. Several lines of evidence indicate that AQP4-Ab not only serves as a disease marker but also plays a pivotal role in the pathogenesis of NMO. Although the pathogenicity of AQP4-Ab in vivo has recently been demonstrated, the presence of CNS antigen-specific T cells is recognized as a prerequisite for the antibody to exert pathogenic effects. Thus, it remains unclear whether AQP4-Ab is the primary cause of the disease or a disease-modifying factor in NMO. Here we report that pre-treatment with complete Freund's adjuvant (CFA) alone is sufficient for AQP4-Ab to induce astrocytic damage in vivo. Our results show the primary pathogenic role of AQP4-Ab in the absence of CNS antigen-specific T cells, and suggest that danger signals provided by nonspecific inflammation can be a trigger for those who harbor the autoantibody to develop NMO.
视神经脊髓炎（NMO）是一种中枢神经系统（CNS）的炎症性脱髓鞘疾病。抗水通道蛋白 4 抗体（AQP4-Ab）是一种高度特异性的血清自身抗体，可在 NMO 患者中检测到。有几条证据表明，AQP4-Ab 不仅是疾病标志物，而且在 NMO 的发病机制中起关键作用。尽管最近已经证明了 AQP4-Ab 在体内的致病性，但中枢神经系统抗原特异性 T 细胞的存在被认为是抗体发挥致病作用的前提。因此，目前尚不清楚 AQP4-Ab 是疾病的主要原因还是 NMO 的疾病修饰因素。在这里，我们报告称，单独使用完全弗氏佐剂（CFA）预处理就足以诱导体内星形胶质细胞损伤。我们的结果表明 AQP4-Ab 在没有中枢神经系统抗原特异性 T 细胞的情况下具有主要的致病性作用，并表明非特异性炎症提供的危险信号可能是那些携带自身抗体的人发展为 NMO 的触发因素。
