ROLE OF ACIDIC GLYCOLIPIDS IN EXPERIMENTAL NEUROPATHY

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Guillain-Barre' syndrome (GBS) is an acute inflammatory demyelinating disease of human peripheral nervous system. The etiology and pathogenesis of GBS remain unknown. Recent studies, however, have shown that more than 60% of patients with GBS have serum autoantibodies against acidic glycolipids such as IM1, a major ganglioside of human nerve myelin. The long term goal of this project is to establish the potential pathological role of antibodies against acidic glycolipids in neuropathy. Our hypothesis is that high titer antibodies to acidic glycolipids in some GBS patients play an important role in the pathogenesis of neuropathy. Rats will be sensitized with purified IM1 and other glycolipids that have been shown to react with GBS patients' autoantibodies. After immunization rat sera will be tested for antibodies to acidic glycolipids by an enzyme- linked immunosorbent assay and a thin-layer chromatography-immunostaining technique and the immunochemical properties of the experimentally produced antibodies will be compared with human autoantibodies. Rats will be assessed for clinical and electrophysiological signs of neuropathy. Peripheral nerves from the sensitized rats will be evaluated for pathologic changes by light and electron microscopy. The pathologic role of anti- acidic glycolipid antibodies in the rat will be further investigated by transfering the disease to normal rats will be compared with that seen in actively immunized animals. The successful transfer of disease by immunoglobulin fractions or affinity purified antibodies will strongly suggest that anti-acidic glycolipid antibodies may have a causal role. An experimental autoimmune neuropathy closely resembling GBS will be a valuable model for studying the pathogenic mechanisms of neuropathy by passive transfer studies and may provide invaluable information for establishing the pathogenesis and possibly the eventual prevention of not only GBS but also other human demyelinating diseases such a multiple sclerosis.