Anti-aquaporin-4 antibody induces astrocytic cytotoxicity in the absence of CNS antigen-specific T cells
Anti-aquaporin-4 antibody induces astrocytic cytotoxicity in the absence of CNS antigen-specific T cells
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DOI：
10.1016/j.bbrc.2010.02.157
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发表时间：
2010-03-26
影响因子：
3.1
通讯作者：
Sakoda, Saburo
中科院分区：
文献类型：
--
作者：
Kinoshita, Makoto;Nakatsuji, Yuji;Sakoda, Saburo
视神经肌萎缩症（NMO）是一种中枢神经系统（CNS）的炎性脱髓鞘疾病。抗水通道蛋白-4抗体（AQP 4-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。多项证据表明，AQP 4-Ab不仅作为疾病标志物，而且在NMO的发病机制中起着关键作用。虽然AQP 4-Ab在体内的致病性最近已被证明，CNS抗原特异性T细胞的存在被认为是抗体发挥致病作用的先决条件。因此，目前尚不清楚AQP 4-Ab是疾病的主要原因还是NMO中的疾病修饰因子。在这里，我们报告说，预处理与完全弗氏佐剂（CFA）单独是足够的AQP 4抗体诱导星形胶质细胞损伤体内。我们的研究结果表明，在缺乏CNS抗原特异性T细胞的情况下，AQP 4-Ab的主要致病作用，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NMO的触发因素。(C)2010年爱思唯尔公司All rights reserved.
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. (C) 2010 Elsevier Inc. All rights reserved.