title: Identification of Epstein-Barr virus proteins as putative targets of the immune response in multiple sclerosis.
abstract: MS is a chronic inflammatory and demyelinating disease of the CNS with as yet unknown etiology. A hallmark of this disease is the occurrence of oligoclonal IgG antibodies in the cerebrospinal fluid (CSF). To assess the specificity of these antibodies, we screened protein expression arrays containing 37,000 tagged proteins. The 2 most frequent MS-specific reactivities were further mapped to identify the underlying high-affinity epitopes. In both cases, we identified peptide sequences derived from EBV proteins expressed in latently infected cells. Immunoreactivities to these EBV proteins, BRRF2 and EBNA-1, were significantly higher in the serum and CSF of MS patients than in those of control donors. Oligoclonal CSF IgG from MS patients specifically bound both EBV proteins. Also, CD8(+) T cell responses to latent EBV proteins were higher in MS patients than in controls. In summary, these findings demonstrate an increased immune response to EBV in MS patients, which suggests that the virus plays an important role in the pathogenesis of disease.
authors.affiliation: Department of Neurology, Heinrich Heine University, Duesseldorf, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Cepok
authors.forename: Dun
authors.initials: D
authors.lastname: Zhou
authors.forename: Rajneesh
authors.initials: R
authors.lastname: Srivastava
authors.forename: Stefan
authors.initials: S
authors.lastname: Nessler
authors.forename: Susanne
authors.initials: S
authors.lastname: Stei
authors.forename: Konrad
authors.initials: K
authors.lastname: Büssow
authors.forename: Norbert
authors.initials: N
authors.lastname: Sommer
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hemmer
mesh_terms: D000906:Antibodies / Q000235:genetics / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000134:cerebrospinal fluid / Q000276:immunology; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D040081:Protein Array Analysis; D013601:T-Lymphocytes / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D000906:Antibodies; D007074:Immunoglobulin G; D014764:Viral Proteins