ROLE OF ACIDIC GLYCOLIPIDS IN EXPERIMENTAL NEUROPATHY

格林-巴利综合征（Guillain-Barre' syndrome，GBS）是一种急性炎症性脱髓鞘 人类周围神经系统疾病。 病因病机 GBS仍然未知。 然而，最近的研究表明， 60%的GBS患者血清中存在抗酸性粒细胞抗体， 糖脂，如IM 1，人神经髓鞘的主要神经节苷脂。 的 该项目的长期目标是建立潜在的病理 抗酸性糖脂抗体在神经病中的作用 我们 假设在某些GBS中酸性糖脂的高滴度抗体 患者在神经病的发病机制中起重要作用。 大鼠 将被纯化的IM 1和其他糖脂敏化， 与GBS患者的自身抗体发生反应 免疫后大鼠 将通过酶检测血清中的酸性糖脂抗体， 连接免疫吸附试验和薄层层析免疫染色 技术和免疫化学性质的实验产生的 将抗体与人自身抗体进行比较。 大鼠将 评估神经病变的临床和电生理体征。 将对致敏大鼠的外周神经进行病理学评价 通过光学和电子显微镜观察变化。 抗- 大鼠中的酸性糖脂抗体将进一步研究， 将疾病转移到正常大鼠中的情况与 积极免疫动物。 成功地将疾病 免疫球蛋白级分或亲和纯化的抗体将强烈地 表明抗酸性糖脂抗体可能具有因果作用。 一个 实验性自身免疫性神经病变密切类似GBS将是一个 为研究神经病变的发病机制提供了一个有价值的模型， 被动转移研究，并可能提供宝贵的信息， 建立发病机制，并可能最终预防非 不仅是GBS，而且还有其他人类脱髓鞘疾病， 硬化症

Guillain-Barre' syndrome (GBS) is an acute inflammatory demyelinating disease of human peripheral nervous system. The etiology and pathogenesis of GBS remain unknown. Recent studies, however, have shown that more than 60% of patients with GBS have serum autoantibodies against acidic glycolipids such as IM1, a major ganglioside of human nerve myelin. The long term goal of this project is to establish the potential pathological role of antibodies against acidic glycolipids in neuropathy. Our hypothesis is that high titer antibodies to acidic glycolipids in some GBS patients play an important role in the pathogenesis of neuropathy. Rats will be sensitized with purified IM1 and other glycolipids that have been shown to react with GBS patients' autoantibodies. After immunization rat sera will be tested for antibodies to acidic glycolipids by an enzyme- linked immunosorbent assay and a thin-layer chromatography-immunostaining technique and the immunochemical properties of the experimentally produced antibodies will be compared with human autoantibodies. Rats will be assessed for clinical and electrophysiological signs of neuropathy. Peripheral nerves from the sensitized rats will be evaluated for pathologic changes by light and electron microscopy. The pathologic role of anti- acidic glycolipid antibodies in the rat will be further investigated by transfering the disease to normal rats will be compared with that seen in actively immunized animals. The successful transfer of disease by immunoglobulin fractions or affinity purified antibodies will strongly suggest that anti-acidic glycolipid antibodies may have a causal role. An experimental autoimmune neuropathy closely resembling GBS will be a valuable model for studying the pathogenic mechanisms of neuropathy by passive transfer studies and may provide invaluable information for establishing the pathogenesis and possibly the eventual prevention of not only GBS but also other human demyelinating diseases such a multiple sclerosis.