Anti-GM2 gangliosides IgM paraprotein induces neuromuscular block without neuromuscular damage.
We analyzed the effect on the mouse neuromuscular synapses of a human monoclonal IgM, which binds specifically to gangliosides with the common epitope [GalNAc beta 1-4Gal(3-2 alpha NeuAc)beta 1-]. We focused on the role of the complement. Evoked neurotransmission was partially blocked by IgM both acutely (1 h) and chronically (10 days). Transmission electron microscopy shows important nerve terminal growth and retraction remodelling though axonal injury can be ruled out. Synapses did not show mouse C5b-9 immunofluorescence and were only immunolabelled when human complement was added. Therefore, the IgM-induced synaptic changes occur without complement-mediated membrane attack.
Santafé
Manel M
MM
Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, carrer St. Llorenç num 21, 43201-Reus, Spain. msm@fmcs.urv.es
Sabaté
M Mar
MM
Garcia
Neus
N
Ortiz
Nico
N
Lanuza
M Angel
MA
Tomàs
Josep
J
D000704:Analysis of Variance; D000818:Animals; D002038:Bungarotoxins / Q000378:metabolism; D002855:Chromatography, Thin Layer / Q000379:methods; D003165:Complement System Proteins / Q000378:metabolism; D003711:Demyelinating Diseases / Q000097:blood / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D020143:Gangliosidoses, GM2 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007075:Immunoglobulin M / Q000494:pharmacology*; D051379:Mice; D008855:Microscopy, Electron, Scanning / Q000379:methods; D055369:Miniature Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D019148:Neuromuscular Blockade; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D010266:Paraproteins / Q000276:immunology* / Q000378:metabolism; D050765:Qa-SNARE Proteins / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism
D002038:Bungarotoxins; D000939:Epitopes; D007075:Immunoglobulin M; D010266:Paraproteins; D050765:Qa-SNARE Proteins; D009418:S100 Proteins; C050974:complement C5b-6 complex; D003165:Complement System Proteins