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

在感染后自身免疫性疾病中，微生物和自身成分之间的分子模仿被认为是解释免疫反应抗原和组织特异性的机制。很少有直接证据存在，并且该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-巴利综合征是急性神经肌肉麻痹的最常见原因，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，这里报道了确凿的证据。空肠假单胞脂寡糖致敏后，家兔产生抗gm1 IgG抗体，四肢无力。瘫痪兔周围神经的病理改变与格林-巴利综合征相同。用脂寡糖免疫小鼠产生与GM1反应并结合人周围神经的单克隆抗体。吉兰-巴利综合征患者的单克隆抗体和抗gm1 IgG阻断肌肉-脊髓共培养的肌肉动作电位，提示抗gm1抗体可引起肌肉无力。这些发现表明碳水化合物模拟是自身免疫性神经病变的一个重要原因。

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.