ACIDIC GLYCOLIPIDS AND EXPERIMENTAL NEUROPATHY

格林-巴利综合征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的数量仍不清楚。然而，最近的研究表明，不仅仅是 60%的GBS患者血清中有抗酸性自身抗体 糖脂，如IM1，人类神经髓鞘的主要神经节苷脂。这个 这个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。我们的 假说是某些GBS中存在高滴度的酸性糖脂抗体 患者在神经病的发病机制中起着重要作用。老鼠 将用纯化的IM1和其他糖脂致敏 被证明与GBS患者的自身抗体发生反应。免疫后大鼠 血清将通过一种酶进行酸性糖脂抗体测试- 联用免疫吸附试验和薄层色谱-免疫染色 技术和实验生产的疫苗的免疫化学性质 抗体将与人类自身抗体进行比较。老鼠将会是 评估神经病变的临床和电生理体征。 将对致敏大鼠的周围神经进行病理学评估 光镜和电子显微镜下的变化。抗-HBs的病理作用 将进一步研究大鼠体内的酸性糖脂抗体 将疾病转移到正常大鼠身上的实验将与 主动免疫的动物。通过以下途径成功转移疾病 免疫球蛋白部分或亲和纯化的抗体将强烈 提示抗酸性糖脂抗体可能起到了因果作用。一个 类似于GBS的实验性自身免疫性神经病将是一种 为研究神经病的发病机制提供有价值的模型 被动转移研究，并可能提供宝贵的信息 确定NOT的发病机制并可能最终预防 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.