ganglioside--gm4 and Multiple-Sclerosis

Antibody titers against myelin constituents in sera and CSF of patients with multiple sclerosis (MS) were examined by a solid-phase radioimmunoassay. Anti-GM4 and anti-galactocerebroside antibody titers were significantly elevated in the CSF of MS patients, but not anti-GM1 and anti-myelin basic protein antibodies. In sera of MS patients, the titers of antibodies against these myelin constituents were not elevated. Total IgG level was also significantly elevated in the CSF, but not in the sera of MS patients. Immune complexes from the CSF of MS patients were dissociated by acid-ultrafiltration and assayed for antibodies to GM4, GM1, and galactocerebroside. Anti-GM4 and antigalactocerebroside antibody titers were significantly enhanced after acid dissociation and ultrafiltration. These data suggest that antibodies of the IgG class against GM4 and galactocerebroside are present in CSF of MS patients, and a significant number of them exist as immune complexes with their corresponding glycolipid antigens.

Topics: Antibody Specificity; Autoantibodies; Brain; G(M1) Ganglioside; Galactosylceramides; Gangliosides; Glycolipids; Humans; Immune Complex Diseases; Immunoglobulin G; Multiple Sclerosis; Myelin Basic Protein; Myelin Proteins; Myelin Sheath; Radioimmunoassay

Demyelinated plaques in multiple sclerosis have decreased amounts of both myelin basic protein and sialosylgalactosylceramide (GM4), a ganglioside specifically localized in myelin and oligodendroglia of the central nervous system. We have found that myelin basic protein is capable of releasing large quantities of entrapped [14C]glucose from multilamellar liposomes containing GM4. If the conformation of GM4 in liposomal membranes resembles that of GM4 in its natural environment, basic protein and GM4 may be associated within the myelin sheath of the central nervous system and their interaction altered in demyelinating diseases such as multiple sclerosis.

Topics: Gangliosides; Glucose; Humans; Immunodiffusion; Kinetics; Lipid Bilayers; Multiple Sclerosis; Myelin Basic Protein; Protein Binding