ROLE OF ACIDIC GLYCOLIPIDS IN EXPERIMENTAL NEUROPATHY

Project Details

Description

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.
StatusFinished
Effective start/end date9/1/918/31/97

Funding

  • National Institutes of Health: $106,859.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Neuroscience(all)

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