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

外周神经髓磷脂，尤其是副神经节髓磷脂，是格林-巴利综合征（GBS）自身免疫机制的靶点。据报道，糖脂类，包括神经节苷类，在急性期GBS血清中经常被抗体识别。我们已经报道了神经节苷脂GD1b特异性定位于人周围神经系统的副神经节髓鞘和初级感觉神经元。本研究显示，抗gd1b IgG抗体的GBS患者比对照GBS患者更常见电生理性脱髓鞘改变和感觉障碍。提示抗GD1b IgG抗体可能与GD1b所在的副神经节髓鞘和初级感觉神经元结合，引起脱髓鞘脱髓鞘和感觉障碍。LM1是人外周髓鞘中主要的神经节苷脂，GBS患者具有针对LM1的IgG抗体，表现为轻度神经问题和电生理性脱髓鞘改变。因此，针对神经节苷的抗体定位于髓鞘，可能与轴突变化无关，而与脱髓鞘有关。在家兔中，GD1b定位于初级感觉神经元，而不定位于副神经节髓鞘。我们用GD1b致敏家兔，诱导实验性感觉性共济失调神经病。在本研究中，我们发现与GM1无交叉反应的抗gd1b抗体可能是该实验性神经病变的重要致病因素。GBS患者急性期血清IgG抗体特异性免疫染色兔外周髓磷脂。兔周围神经特异性免疫染色兔雪旺细胞免疫小鼠产生的单克隆抗体。需要鉴定这些抗体的抗原分子。这些抗原可能有助于诱导具有脱髓鞘改变的GBS动物模型，从而了解GBS的发病机制并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.