Investigation on the pathogenetic mechanism of GD1b-induced experimental neuropathy and approach to effective treatment

抗神经节苷脂抗体在自身免疫性神经病患者的血清中经常升高。它们可能作为自身抗体参与发病机制。我们已经报道了用定位于初级感觉神经元的神经节苷脂GD1b致敏兔诱导实验性感觉性失调性神经病变。病理观察到传递深层感觉的初级感觉神经元轴突变性。抗gd1b抗体高滴度升高且无淋巴细胞浸润提示抗gd1b抗体是诱导该实验性神经病变的关键因素。即使在早期临床前期也未发现淋巴细胞浸润。IgM类抗gd1b抗体在第一次免疫后4周达到峰值。IgG抗体随之升高。在那之后，神经系统症状出现了。gd1b阳性的初级感觉神经元直径较大。一只兔在神经症状好转后又再次恶化，随访5个月。抗gd1b抗体与临床病程相关。频繁采血的3只感染兔，抗体效价下降，临床表现明显改善。因此，抗gd1b抗体（特别是IgG类）与传递深层感觉的大初级感觉神经元的结合可能是这种实验性神经病变发病机制的重要步骤。去除抗gd1b抗体可能对治疗这种神经病变有效。

Antiganglioside antibodies are frequently elevated in sera from patients with autoimmune neuropathies. They may be involved in the pathogenetic mechanisms as autoantibodies. We have reported induction of experimental sensory ataxic neuropathy by sensitization of rabbits with ganglioside GD1b, which are localized in the primary sensory neurons. Axonal degeneration of the primary sensory neurons conveying deep sensation was observed pathologically. Elevation of anti-GD1b antibody in high titer and absence of lymphocytic infiltration suggested that anti-GD1b antibody is the crucial factor for induction of this expermental neuropathy. Lymphocytic infiltration was not detected even in the early preclinical period. Anti-GD1b antibody of IgM class reached the peak level in four weeks after the first immunization. The elevation of the IgG antibody followed that. The neurological signs developed after that. GD1b-positive primary sensory neurons were with large diameters. One rabbit which were followed for 5 months after the neurological onset improved and again worsened. THe anti-GD1b antibody decreased and increased in association with the clinical course. In the three affected rabbits from which blood was taken frequently, the antibody titer decreased and the clinical findings improved markedly. The binding of the anti-GD1b antibody(especially the IgG class)to the large primary sensory neurons, which convey deep sensation, therefore may be the important step in the pathogenesis of this experimental neuropathy. Removal of anti-GD1b antibody may be effective for the treatment of this neuropathy.