Monoclonal antibodies raised against Guillain-Barre syndrome-associated Campylobacter jejuni lipopolysaccharides react with neuronal gangliosides andparalyze muscle-nerve preparations

Guillain-Barre syndrome and its variant, Miller-Fisher syndrome, are acute, postinfectious, autoimmune neuropathies that frequently follow Campylobact er jejuni enteritis. The pathogenesis is believed to involve molecular mimi cry between sialylated epitopes on C. jejuni LPSs and neural gangliosides. More than 90% of Miller-Fisher syndrome cases have serum anti-GQ1b and anti -GT1a ganglioside antibodies that may also react with other disialylated ga ngliosides including GD3 and GD Ib. Structural studies on LPS from neuropat hy-associated C. jejuni strains have revealed GT1a-like and GD3-like core o ligosaccharides. To determine whether this structural mimicry results in pa thogenic autoantibodies, we immunized mice with GT1a/GD3-like C. jejuni LPS and then cloned mAb's that reacted with both the immunizing LPS and GQ1b/G T1a/GD3 gangliosides. Immunohistology demonstrated antibody binding to gang lioside-rich sites including motor nerve terminals. In ex vivo electrophysi ological studies of nerve terminal function, application of antibodies eith er ex vivo or in vivo via passive immunization induced massive quantal rele ase of acetylcholine, followed by neuro-transmission block. This effect was complement-dependent and associated with extensive deposits of IgM and C3c at nerve terminals. These data provide strong support for the molecular mi micry hypothesis as a mechanism for the induction of cross-reactive pathoge nic anti-ganglioside/LPS antibodies in postinfectious neuropathies.