galactocerebroside and Motor-Neuron-Disease

IgM anti-GM1 antibodies are associated with motor neuropathy syndromes, including multifocal motor neuropathy (MMN). We compared the ability of serum IgM from patients with multifocal motor neuropathy to bind to GM1 ganglioside alone and to GM1 as a component of a lipid mixture that also contained galactocerebroside and cholesterol (GGC). Our results showed that high-titer selective serum IgM binding to GGC has strong specificity for MMN. Further, over 40% more serums from patients with MMN have high-titer serum IgM binding to GGC than to GM1 alone. The specific composition and structure of the lipid mixture altered the ability of serum IgM to bind to GM1 ganglioside. Substitutions of other lipids for galactocerebroside or cholesterol could completely inhibit the antibody binding. We conclude that serum IgM anti-GGC autoantibodies have specificity for MMN and their binding is strongly influenced by the lipid environment of GM1 ganglioside.

Topics: Cholesterol Esters; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Galactosylceramides; Humans; Immunoglobulin M; Lipids; Motor Neuron Disease; Sensitivity and Specificity

Anti-galactocerebroside (GalC) antibodies have been reported to inhibit myelin formation, cause demyelination, and block HIV-I infection of neural cells. We examined the binding of 3 monoclonal and polyclonal anti-GalC antibodies to a panel of purified glycolipids by ELISA and by an immunospot assay on nitrocellulose blots. All 3 antibodies bound strongly to GM1 ganglioside, monogalactosyl diglyceride, and asialo-GM1, and 2 of the antibodies bound to GD1b and psychosine. The anti-GalC antibodies also bound to 3 glycoprotein bands in human neuroblastoma cells on Western blot, and binding to the proteins was abolished by pre-treatment with pronase or with periodate which oxidizes the terminal carbohydrate residues. These results indicate that anti-GalC antibodies cross react with oligosaccharide determinants of other glycolipids and glycoproteins, and that these cross-reactivities may be responsible for some of the biological effects of the anti-GalC antibodies.

Topics: Animals; Antibody Specificity; Antigens, Neoplasm; Autoantibodies; Carbohydrate Sequence; Cross Reactions; Enzyme-Linked Immunosorbent Assay; Epitopes; Galactosylceramides; Glycolipids; Glycoproteins; Humans; Immunoglobulin M; Mice; Molecular Sequence Data; Motor Neuron Disease; Neoplasm Proteins; Neuroblastoma; Rabbits; Sensation Disorders; Tumor Cells, Cultured

High titers of serum antibodies against GM1 ganglioside occur frequently in patients with lower motor neuron (LMN) syndromes. We compared the specificities of the antiganglioside antibody reactivities in LMN patients with those arising after immunization of Lewis rats with several ganglioside containing preparations including purified GM1, human central nervous system (CNS) grey matter and white matter. Serums with high titers of anti-GM1 antibodies from patients with LMN syndrome usually showed limited cross-reactivity to other glycolipids but often bound to a Gal(beta 1-3)GalNAc-containing neoglycoprotein. In contrast, serums with anti-GM1 antibody arising after immunization showed broad cross-reactivity with other glycolipids but did not bind to the neoglycoprotein. We conclude that the serum patterns of antiganglioside antibody reactivity secondary to immunization with gangliosides and CNS components are different from the natural autoantibodies found in LMN patients. The antiganglioside antibodies seen in LMN patients are unlikely to be a result of autoreactivity to gangliosides after nervous tissue damage.

Topics: Animals; Brain; Female; G(M1) Ganglioside; Galactosylceramides; Glycoproteins; Immunization; Immunoglobulin G; Motor Neuron Disease; Peripheral Nerves; Rats; Rats, Inbred Lew