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.
Li
F
F
Department of Neurology, IWJ Institute of Rehabilitation, Washington University School of Medicine, St. Louis, MO 63110.
Pestronk
A
A
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