Human gangliosides and bacterial lipo-oligosaccharides in the development of autoimmune neuropathies.

Abstract

Guillain-Barré syndrome (GBS), the most frequent cause of acute flaccid paralysis, can develop after infection by Campylobacter jejuni. The condition is often associated with serum anti-GM1 or anti-GD1a IgG antibodies. Gangliosides contribute to stability of paranodal junctions and ion channel clusters in myelinated nerve fibers. Autoantibodies to GM1 and GD1a disrupt lipid rafts, paranodal or nodal structures, and ion channel clusters in peripheral motor nerves. Molecular mimicry exists between GM1 and GD1a gangliosides and lipo-oligosaccharides of C. jejuni isolates from GBS patients. Sensitization of rabbits with GM1 or C. jejuni lipo-oligosaccharide produces replica of GBS. These findings provide strong evidence for carbohydrate mimicry being a cause of GBS and show the role of gangliosides in peripheral nerves.