Anti-ganglioside antibodies and the presynaptic motor nerve terminal.
The Guillain Barré syndromes (GBS) are the world's leading cause of acute autoimmune neuromuscular paralysis. Understanding the pathophysiological events of GBS, and improving immunotherapies are fundamental to improving the clinical outcome. Recent research into GBS and the Miller Fisher syndrome (MFS) variant has focused on the forms mediated by anti-ganglioside antibodies in which correlations have been established between anti-ganglioside antibodies and specific clinical phenotypes, notably between anti-GM1/GD1a antibodies and the acute motor axonal variant and anti-GQ1b/GT1a antibodies and MFS. Anti-ganglioside antibodies can arise through molecular mimicry with GBS-associated Campylobacter jejuni oligosaccharides. Our work has focused on axonal and glial components of the motor nerve terminal as a model site of injury, and through combined active and passive immunization paradigms in glycosyltransferase knockout mice we have developed murine neuropathy phenotypes mediated by anti-ganglioside antibodies. Several determinants influence disease expression including the level of immunological tolerance to microbial glycans that mimic self gangliosides, the degree of complement activation, and the ganglioside density in target tissue. Such studies provide us with clear information on an antibody-mediated pathogenesis model for GBS and should lead to rational therapeutic testing of agents that are potentially suitable for use in man.
Division of Clinical Neurosciences, University of Glasgow , Scotland, UK. h.j.willison@clinmed.gla.ac.uk
Hugh J
HJ
Willison
Jaap J
JJ
Plomp
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D003165:Complement System Proteins / Q000378:metabolism; D005732:Gangliosides / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D019846:Miller Fisher Syndrome / Q000276:immunology / Q000378:metabolism; D009046:Motor Neurons / Q000276:immunology* / Q000378:metabolism*; D013569:Synapses / Q000276:immunology* / Q000378:metabolism*
D000906:Antibodies; D005732:Gangliosides; D003165:Complement System Proteins