Molecular mimicry between microbial and self-components is postulated as the mechanism that accounts for the
antigen and tissue specificity of immune responses in postinfectious
autoimmune diseases. Little direct evidence exists, and research in this area has focused principally on T cell-mediated, antipeptide responses, rather than on humoral responses to
carbohydrate structures.
Guillain-Barré syndrome, the most frequent cause of acute neuromuscular
paralysis, occurs 1-2 wk after various
infections, in particular, Campylobacter jejuni
enteritis.
Carbohydrate mimicry [Galbeta1-3GalNAcbeta1-4(NeuAcalpha2-3)Galbeta1-] between the bacterial lipooligosaccharide and human
GM1 ganglioside is seen as having relevance to the pathogenesis of
Guillain-Barré syndrome, and conclusive evidence is reported here. On sensitization with C. jejuni lipooligosaccharide, rabbits developed anti-GM1
IgG antibody and flaccid limb weakness. Paralyzed rabbits had pathological changes in their peripheral nerves identical with those present in
Guillain-Barré syndrome. Immunization of mice with the lipooligosaccharide generated a mAb that reacted with GM1 and bound to human peripheral nerves. The mAb and anti-GM1
IgG from patients with
Guillain-Barré syndrome did not induce
paralysis but blocked muscle action potentials in a muscle-spinal cord coculture, indicating that anti-GM1 antibody can cause
muscle weakness. These findings show that
carbohydrate mimicry is an important cause of autoimmune neuropathy.