Pathogenesis of Guillain-Barre syndrome and Fisher syndromes : evidence of molecular mimicry

微生物和自身组分之间的分子模拟被假定为解释感染后自身免疫性疾病中免疫应答的抗原和组织特异性的机制。几乎没有直接的证据存在，在这方面的研究主要集中在T细胞介导的，抗肽反应，而不是对碳水化合物结构的体液反应。格林-巴利综合征是急性神经肌肉麻痹最常见的原因，发生在各种细菌和病毒感染后1至2周，特别是空肠弯曲杆菌肠炎。细菌脂寡糖和人GM 1神经节苷脂之间的碳水化合物模拟被认为与格林-巴利综合征的发病机制有关，这里报道了确凿的证据。用空肠弯曲菌脂寡糖致敏后，家兔产生抗GM 1 IgG抗体，并出现四肢无力。麻痹家兔的周围神经发生了与格林-巴利综合征相同的病理变化。用脂寡糖免疫小鼠产生了一种单克隆抗体，该抗体与GM 1反应并与人类外周神经结合。来自格林-巴利综合征患者的单克隆抗体和抗GM 1 IgG阻断了肌肉-脊髓共培养物中的肌肉动作电位，表明抗GM 1抗体可导致肌无力。这些发现表明碳水化合物拟态是自身免疫性神经病的重要原因。

Molecular mimicry between microbial and self components is postulated as the mechanism that accounts for the antigen and tissue specificity of immune responses in post-infectious autoimmune diseases. Little direct evidence exists, and research in this area has focused principally on T cell-mediated, anti-peptide responses, rather than on humoral responses to carbohydrate structures. Guillain-Barre syndrome, the most frequent cause of acute neuromuscular paralysis, occurs 1 to 2 weeks after various bacterial and viral infections, particularly Campylobacter jejuni enteritis. Carbohydrate mimicry between the bacterial lipo-oligosaccharide and human GM1 ganglioside is seen as having relevance to the pathogenesis of Guillain-Barre syndrome, and conclusive evidence is reported here. On sensitization with C.jejuni lipo-oligosaccharide, rabbits developed anti-GM1 IgG antibody and flaccid limb weakness. Paralyzed rabbits had pathological changes in their peripheral nerves identical to those present in Guillain-Barre syndrome. Immunization of mice with the lipo-oligosaccharide generated a monoclonal antibody that reacted with GM1 and bound to human peripheral nerves. The monoclonal antibody and anti-GM1 IgG from patients with Guillain-Barre syndrome blocked muscle action potentials in a muscle-spinal cord co-culture, indicative that anti-GM1 antibody can cause muscle weakness. These findings show that carbohydrate mimicry is an important cause of autoimmune neuropathy.