galactocerebroside and Multiple-Sclerosis

According to the molecular mimicry theory, multiple sclerosis (MS) develops when the immune system mistakenly attacks a component of the myelin sheath that is structurally similar to a foreign epitope. The glycolipid galactocerebroside (GalC) is a major component of myelin. As lipids comprise between 70% and 85% of myelin, glycolipids should be investigated as candidate autoantigens in MS. GalC displays broad structural similarities to the Borrelia burgdorferi glycolipid antigen BbGL-2 and to the Sphingomonas antigen GalAGSL. In principle, therefore, these bacteria may induce an autoimmune attack on the myelin sheath. GalC is also structurally similar to natural killer T (NKT) cell ligand alpha-galactosylceramide (alpha-GalCer). Further studies must be performed to clarify the role of GalC in the activation of NKT cells and the development of MS.

Topics: Animals; Autoimmunity; Borrelia burgdorferi; Galactosylceramides; Glycolipids; Humans; Killer Cells, Natural; Ligands; Models, Biological; Models, Chemical; Models, Theoretical; Multiple Sclerosis; Myelin Sheath; Sphingomonas

Galactocerebroside, the major glycolipid of central nervous system myelin, is a known target for pathogenic demyelinating antibody responses in experimental allergic encephalomyelitis (EAE), the animal model of multiple sclerosis (MS).. To address the importance of anti-galactocerebroside (alpha-GalC) antibodies in MS and to evaluate them as biomarkers of disease.. alpha-GalC IgGs were quantified from sera of patients with MS and in marmoset EAE by a new immunosorbent assay.. We report a significant difference in serum alpha-GalC IgG titers between patients with relapsing-remitting (RR)-MS and healthy controls (HCs; P < .001). The frequencies of alpha-GalC antibody-positive subjects (alpha-GalC titers > or = mean HC titers+3 SD) are also significantly elevated in RR-MS compared with HC (40% vs 0%; P = .0033). Immunoaffinity purified alpha-GalC IgGs from human serum bind to cultured human oligodendrocytes, indicating that the ELISA detects a biologically relevant epitope. Corroborating these findings, alpha-GalC antibody responses in marmoset EAE were similarly found to be specifically associated with the RR forms and not the peracute or progressive forms, in contrast with other anti-myelin antibodies (P = .0256).. (1) alpha-GalC antibodies appear MS-specific and are not found in healthy subjects, unlike antibodies against myelin proteins; (2) when present, alpha-GalC antibodies identify mostly RR-MS and may be an indicator of ongoing disease activity. This novel assay is a suitable and valuable method to increase accuracy of diagnosis and disease staging in MS.

Topics: Adult; Aged; Animals; Biomarkers; Callithrix; Encephalomyelitis, Autoimmune, Experimental; Enzyme-Linked Immunosorbent Assay; Female; Galactosylceramides; Humans; Immunoglobulin G; Immunohistochemistry; Male; Middle Aged; Multiple Sclerosis

Implantation of hybridoma cells that secrete a monoclonal antigalactocerebroside into the dorsal columns of < or = 9-day-old rat spinal cord results in failure of development of dorsal column myelin in the vicinity of the implant. Clusters of apparently undamaged amyelinated axons remain among the hybridoma cells. Ventral myelin is unaffected. These in vivo results support antibody-mediated inhibition of myelin formation as a potential mechanism underlying failure of remyelination in multiple sclerosis.

Topics: Animals; Antibodies, Monoclonal; Axons; Cytoplasm; Galactosylceramides; Hybridomas; Microscopy, Electron; Multiple Sclerosis; Myelin Sheath; Oligodendroglia; Rats; Rats, Wistar; Spinal Cord

Subacute sclerosing panencephalitis (SSPE) patients carry persistent measles virus infection in the brain. Furthermore, the blood lymphocytes contain viral RNA. Lymphocytes derived from 6 SSPE patients were stimulated with Epstein-Barr virus (EBV). Production of antibodies against measles virus of the IgG isotype was detected in the supernatants of cell cultures of all patients, regardless of the disease's activity, duration or interferon therapy. In contrast, only some of these cell cultures also produced antibodies against myelin.

Topics: Adolescent; Adult; Antibodies, Viral; Antibody Specificity; B-Lymphocytes; Cell Line, Transformed; Cells, Cultured; Child; Encephalitis; Female; Galactosylceramides; Herpesvirus 4, Human; Humans; Immunoglobulin G; Lymphocyte Activation; Male; Measles virus; Multiple Sclerosis; Myelin Basic Protein; Pregnancy; Pregnancy Complications, Infectious; Subacute Sclerosing Panencephalitis

Rubella virus multiplied to low titre and produced a partial cytopathic effect in rat glial cell cultures. Anti-galactocerebroside staining showed that this cytopathic effect involved the disintegration of oligodendrocytes. A similar effect was produced following infection of myelinating neural cell cultures with rubella virus, but virus multiplication could not be detected in pure neuron cultures. Measles virus was found to multiply and produce a cytopathic effect in primary cultures of both neurons and glial cells. These results are discussed in relation to the ability of measles and rubella viruses to trigger human multiple sclerosis.

Topics: Animals; Antibodies; Cells, Cultured; Galactosylceramides; Measles virus; Multiple Sclerosis; Neuroglia; Neurons; Rats; Rubella virus; Staining and Labeling; Virus Replication