Autoantibodies to GM1 ganglioside: different reactivity to GM1-liposomes in amyotrophic lateral sclerosis and lower motor neuron disorders.
We studied the ability of anti-GM1 ganglioside antibodies to bind to GM1 in a lipid, "membrane-like" environment. Liposomes containing GM1 were synthesized to simulate this environment. We then compared the binding of anti-GM1 a autoantibodies to GM-1-liposomes and to purified GM1. Antibody binding was quantitated using enzyme-linked immunosorbent assay methodology. Our results showed a 250-fold variation in the ability of anti-GM1 antibodies to bind to GM1-liposomes. There was no correlation between GM-1-liposome binding and the carbohydrate specificities of the anti-GM1 antibodies. However, anti-GM1 antibodies from patients with amyotrophic lateral sclerosis (ALS) showed a 4 fold greater binding to GM1-liposomes than antibodies from patients with lower motor neuron (LMN) syndromes. We conclude that a lipid, presumably "membrane-like", environment may greatly influence the degree of anti-GM1 antibody binding to GM1. The low levels of anti-GM1 antibody binding to GM1-liposomes in patients with LMN syndromes may provide a diagnostic means for distinguishing these patients from those with ALS. Anti-GM1 antibodies from patients with ALS may bind especially well to neuronal membranes containing GM1 in vivo.
Department of Neurology, IWJ Institute of Rehabilitation, Washington University School of Medicine, St. Louis, MO 63110.
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D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D005677:G(M1) Ganglioside / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000032:analysis; D008081:Liposomes; D016472:Motor Neuron Disease / Q000097:blood / Q000276:immunology*
D001323:Autoantibodies; D007075:Immunoglobulin M; D008081:Liposomes; D005677:G(M1) Ganglioside