Identification of a ganglioside localized in paranodal region of peripheral nerve and induction of experimental autoimmune neuropathy

周围神经髓鞘，尤其是结旁髓鞘，是格林-巴利综合征(GBS)自身免疫机制的靶点。据报道，包括神经节苷脂在内的糖脂经常被急性期血清中的抗体识别。我们已报道神经节苷脂GD1b特异性地定位于人周围神经系统的结旁髓鞘和初级感觉神经元。目前的研究表明，抗GD1b抗体阳性的GBS患者较对照组GBS患者更易出现电生理脱髓鞘改变和感觉障碍。提示抗GD1b抗体可与GD1b定位的结旁髓鞘和初级感觉神经元结合，引起脱髓鞘和感觉障碍。抗人外周髓鞘中主要神经节苷脂LM1抗体阳性的GBS患者表现出轻微的神经系统问题和电生理脱髓鞘改变。因此，定位于髓鞘中的抗神经节苷脂抗体可能不是与轴突改变有关，而是与脱髓鞘有关。在兔中，GD1b定位于初级感觉神经元，而不定位于结旁髓鞘。我们用GD1b致敏兔，并诱导实验性感觉性共济失调神经病。在目前的研究中，我们发现抗GD1b抗体与GM1不发生交叉反应，可能是这种实验性神经病变的关键致病因素。GBS急性期患者血清中特异性免疫染色的兔外周髓鞘抗体。用兔外周神经免疫的小鼠产生的一种单抗，免疫染色的兔雪旺细胞。这是识别这些抗体的抗原分子所必需的。这些抗原可能有助于建立GBS脱髓鞘改变的动物模型，有助于了解GBS的发病机制和开发有效的治疗方法。

Peripheral nerve myelin, especially paranodal myelin, is a target for autoimmune mechanisms in Guillain-Barre syndrome (GBS). It has been reported that glycolipids, including gangliosides, are frequently recognized by antibodies in the acute phase GBS sera. We have reported that ganglioside GD1b is specifically localized in the paranodal myelin and in the primary sensory neurons in human peripheral nervous system. The present investigation showed that electrophysiologically demyelinative changes and sensory disturbances are more common in GBS patients with anti-GD1b IgG antibody than control GBS patients. It indicates that anti-GD1b IgG antibody may bind to paranodal myelin and primary sensory neurons, where GD1b is localized, and cause demyelination and sensory disturbances. GBS patients with IgG antibody against LM1, which is a major ganglioside in human peripheral myelin, showed mild neurological problems and electrophysiologically demyelinative changes. Antibodies against gangliosides that are localized in myelin therefore may be associated not with axonal changes but with demyelination. In rabbits, GD1b is localized in primary sensory neurons but not in paranodal myelin. We have sensitized rabbits with GD1b and induced experimental sensory ataxic neuropathy. In the present investigation we found that anti-GD1b antibody that is not cross-reactive with GM1 may be a crucial pathogenetic factor in this experimental neuropathy. IgG antibodies in sera from GBS patients in the acute phase specifically immunostained rabbit peripheral myelin. A monoclonal antibody produced in mice immunized with rabbit peripheral nerve specifically immunostained rabbit Schwann cells. It is needed to identify the antigen molecules for those antibodies. Those antigens may be useful for inducing animal model of GBS with demyelinative change, leading to understanding pathogenetic mechanisms of GBS and development of effective treatment.