[Pathogenetic mechanism of experimental autoimmune neuropathy induced by sensitization with a ganglioside]

Antiganglioside antibodies are frequently present in sera from patients with autoimmune neuropathies. To elucidate the pathogenetic mechanisms of autoimmune neuropathies mediated by antiganglioside antibodies, we established a rabbit model of sensory ataxic neuropathy induced by sensitization with ganglioside GD1b (GD1b-SAN). Degeneration of primary sensory neurons extending the central axons to the dorsal column of spinal cord was observed pathologically. No lymphocytic cell infiltration was seen. Anti-GD1b antibody therefore should be an essential factor to induce GD1b-SAN. In sera from rabbits immunized with GD1b, two types of antibodies were present; antibodies monospecific to GD 1 b and those cross-reactive with GM1. Of 22 rabbits sensitized with GD1b, 12 developed GD1b-SAN. The level of IgG antibody monospecific to GD1b was higher in the sera from affected rabbits than in those from unaffected ones. The GD1b-positive neuronal cytoplasms of rabbit dorsal root ganglia had larger diameters than the GD1b-negative ones. Markedly reduced expression of trkC in dorsal root ganglia from rabbits with GD1b-SAN in acute phase was found. IgG antibody monospecific to GD1b may cause GD1b-SAN by preferentially binding to large primary sensory neurons mediating proprioceptive sensation. Anti-GD1b antibody-mediated downregulation of trkC expression could be one of the pathogenesis of GD 1 b-SAN.