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

周围神经髓鞘，特别是结旁髓鞘，是格林-巴利综合征（GBS）自身免疫机制的靶点。据报道，糖脂，包括神经节苷脂，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GD 1b特异性定位于人周围神经系统的结旁髓鞘和初级感觉神经元。目前的调查表明，电生理脱髓鞘的变化和感觉障碍是更常见的GBS患者与抗GD 1b IgG抗体比对照GBS患者。这表明抗GD 1b IgG抗体可能与GD 1b定位的结旁髓鞘和初级感觉神经元结合，并引起脱髓鞘和感觉障碍。GBS患者IgG抗体对LM 1，这是一种主要的神经节苷脂在人类外周髓鞘，表现出轻微的神经系统问题和电生理脱髓鞘的变化。因此，定位于髓鞘中的抗神经节苷脂抗体可能与轴突变化无关，而与脱髓鞘有关。在家兔中，GD 1b定位于初级感觉神经元，但不在结旁髓鞘中。我们用GD 1b致敏家兔，并诱导实验性感觉共济失调性神经病。在本研究中，我们发现，抗GD 1b抗体，不与GM 1交叉反应，可能是一个重要的致病因素，在这个实验性神经病。急性期GBS患者血清中的IgG抗体特异性免疫染色兔外周髓鞘。用兔周围神经免疫小鼠产生的单克隆抗体特异性免疫染色兔雪旺细胞。需要鉴定这些抗体的抗原分子。这些抗原可用于诱导GBS脱髓鞘病变的动物模型，从而了解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.