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

微生物和自身成分之间的分子模拟被认为是感染后自身免疫性疾病中免疫反应的抗原和组织特异性的机制。几乎没有直接证据，这一领域的研究主要集中在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-巴利综合征是最常见的急性神经肌肉麻痹的原因，发生在各种细菌和病毒感染，特别是空肠弯曲菌肠炎后1-2周。细菌脂低聚糖和人GM1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，并报告了确凿的证据。空肠弯曲菌脂低聚糖致敏后，兔出现抗GM1抗体，出现肢体无力。瘫痪兔周围神经的病理变化与格林-巴利综合征相同。用这种低聚脂糖免疫小鼠，会产生一种与GM1反应并结合到人类周围神经上的单抗。格林-巴利综合征患者的单抗和抗GM1抗体阻断了肌肉-脊髓共培养的肌肉动作电位，表明抗GM1抗体可导致肌肉无力。这些发现表明，碳水化合物模仿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.