title: Detection and prevalence of alpha-latrotoxin-like effects of serum from patients with Guillain-Barré syndrome.
abstract: Anti-GQ1b antibodies are associated with the Miller Fisher syndrome (MFS), a variant of the Guillain-Barré syndrome (GBS). In the ex vivo mouse diaphragm, anti-GQ1b-positive MFS serum induces muscle fiber twitching, a temporary dramatic increase of spontaneous quantal acetylcholine release, and transmission blockade at neuromuscular junctions (NMJs). These effects resemble those of alpha-latrotoxin (alpha-LTx) and are induced by antibody-mediated activation of complement. We developed an assay for detection of the alpha-LTx-like effect, using muscle fiber twitching as indicator. We tested 89 serum samples from GBS, MFS, and control subjects, and studied correlations with clinical signs, anti-ganglioside antibodies, micro-electrode physiology, and complement deposition at NMJs. Twitching was observed with 76% of the MFS and 10% of the GBS samples. It was associated with ophthalmoplegia and anti-GQ1b antibodies in patients, and with increased spontaneous acetylcholine release and C3c-deposition at mouse NMJs. This study strongly suggests that antibodies to GQ1b (with cross-reactivity to related gangliosides) are responsible for the alpha-LTx-like activity. The twitching assay is an efficient test for detection of this effect, and allows for screening of large numbers of samples and modifying drugs.
authors.affiliation: Departments of Neurology and Immunology, Erasmus Medical Center Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. jacob@neur.azr.nl
authors.forename: Bart C
authors.initials: BC
authors.lastname: Jacobs
authors.forename: Roland W M
authors.initials: RW
authors.lastname: Bullens
authors.forename: Graham M
authors.initials: GM
authors.lastname: O'Hanlon
authors.forename: C Wim
authors.initials: CW
authors.lastname: Ang
authors.forename: Hugh J
authors.initials: HJ
authors.lastname: Willison
authors.forename: Jaap J
authors.initials: JJ
authors.lastname: Plomp
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001681:Biological Assay / Q000379:methods*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D019846:Miller Fisher Syndrome / Q000097:blood* / Q000276:immunology / Q000503:physiopathology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D015588:Observer Variation; D013111:Spider Venoms / Q000633:toxicity*
chemical_list: D001323:Autoantibodies; D005732:Gangliosides; D013111:Spider Venoms; C020763:alpha-latrotoxin; C039129:GQ1b ganglioside