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自己抗体による末梢神経疾患の発症機序

自身抗体引起的周围神经疾病的发病机制

基本信息

批准号：
08458252
负责人：
HANDA Shizuo
金额：
$ 4.54万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

Glycosphingolipids are constituents of nerve cells that may serve as important antigens prticipating in humoral and cellular immune responses. Antibodies to glycolipids have been shown to be present in patients with variety of immune-mediated neurological disorders. In this research, we aimed to elucidate the significance of these autoantibodies and the roles of unique family of glycolipids as well as mechanisms that may under lie the immunopathogenesis of these disorders.High anti-ganglioside antibodies titers are detected in patients suffering this disorders. We have demonstrated that gangliosides, which possess a common carbohydrate epitope with bacteria of the preceding infection are potential target antigens for the Guillain-Barre syndrome and Fisher disease. Various minor gangliosides can also be the target of antibodies in many other peripheral neuropathies. In patients with chronic inflammatory demyelinating polyneuropathy, high titer anti-sulfated glucuronosyl glycolipids were frequently detected. This high titer of antibody was not related with the presence of M-protein nor serum IgM value. We propose that polyneuropathy with IgM anti MAG/SGPG antibody form a subgroup of CIDP.Serum anti-glycolipids antibody activities in patients with Meniere's disease showed positive anti-sialylparagloboside antibody titers. by the chemical analysis of acoustic neurinoma samples, neolacto-series glycolipids were detected. These results indicate the significant roles of the anti-glycolipid antibody for the immunopathogenesis of these disorders.

鞘糖脂是神经细胞的组成部分，可作为重要的抗原参与体液免疫和细胞免疫反应。糖脂抗体已被证明存在于各种免疫介导的神经疾病患者中。在这项研究中，我们旨在阐明这些自身抗体的意义和独特的糖脂家族的作用以及这些疾病的免疫发病机制。我们已经证明，神经节苷脂与先前感染的细菌具有共同的碳水化合物表位，是格林-巴利综合征和Fisher病的潜在靶抗原。在许多其他周围神经病中，各种微小的神经节苷脂也可以成为抗体的靶点。在慢性炎症性脱髓鞘多神经病患者中，经常检测到高滴度的抗硫酸葡萄糖醛酸基糖脂。这种高滴度的抗体与M蛋白的存在或血清中的IgM值无关。我们认为，伴有IgM抗MAG/SGPG抗体的多发性神经病是CIDP的一个亚群。梅尼埃病患者的血清抗糖脂抗体活性显示抗唾液酸副糖苷抗体效价阳性。通过听神经瘤标本的化学分析，检测到新乳糖系列糖脂。这些结果表明，抗糖脂抗体在这些疾病的免疫发病机制中具有重要作用。