title: Complex gangliosides as autoantibody targets at the neuromuscular junction in Miller Fisher syndrome: a current perspective.
abstract: Glycosphingolipid biology has increasingly interfaced with the field of human autoimmune neuropathy over the last two decades. There are currently over 20 distinct glycolipids that have been identified as autoantibody targets in a wide range of clinical neuropathy syndromes. This review sets out the clinical and experimental background to one interesting example of anti-glycolipid antibody-associated neuropathy termed Miller Fisher syndrome. This syndrome, comprising the triad of ataxia, areflexia, and ophthalmoplegia, correlates highly with the presence of serum anti-GQ1b antibodies, arising through molecular mimicry with microbial oligosaccharides. Anti-GQ1b antibodies mediate neural injury through binding to GQ1b-enriched sites in the peripheral nervous system, including extraocular nerves. Animal experimental evidence, along with a hypothetical background, indicates the motor nerve terminal may be a key site for anti-GQ1b antibody binding with consequent defects in synaptic transmission, as occurs in botulism and other toxinopathies. Our work in recent years on this hypothesis is summarized.
authors.affiliation: University Department of Neurology, Institute of Neurological Sciences, Southern General Hospital, Glasgow, Scotland, United Kingdom.
authors.forename: Graham M
authors.initials: GM
authors.lastname: O'Hanlon
authors.forename: Roland W M
authors.initials: RW
authors.lastname: Bullens
authors.forename: Jaap J
authors.initials: JJ
authors.lastname: Plomp
authors.forename: Hugh J
authors.initials: HJ
authors.lastname: Willison
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D019846:Miller Fisher Syndrome / Q000276:immunology* / Q000503:physiopathology; D009469:Neuromuscular Junction / Q000276:immunology*; D009435:Synaptic Transmission
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D005732:Gangliosides