title: Intrathecal immune responses to EBV in early MS.
abstract: EBV has been consistently associated with MS, but its signature in the CNS has rarely been examined. In this study, we assessed EBV-specific humoral and cellular immune responses in the cerebrospinal fluid (CSF) of patients with early MS, other inflammatory neurological diseases (OIND) and non-inflammatory neurological diseases (NIND). The neurotropic herpesvirus CMV served as a control. Virus-specific humoral immune responses were assessed in 123 consecutive patients and the intrathecal recruitment of virus-specific antibodies was expressed as antibody indexes. Cellular immune responses tested in the blood of 55/123 patients were positive in 46/55. The CD8(+) CTL responses of these 46 patients were assessed in the blood and CSF using a CFSE-based CTL assay. We found that viral capsid antigen and EBV-encoded nuclear antigen-1, but not CMV IgG antibody indexes, were increased in early MS as compared with OIND and NIND patients. There was also intrathecal enrichment in EBV-, but not CMV-specific, CD8(+) CTL in early MS patients. By contrast, OIND and NIND patients did not recruit EBV- nor CMV-specific CD8(+) CTL in the CSF. Our data, showing a high EBV-, but not CMV-specific intrathecal immune response, strengthen the association between EBV and MS, in particular at the onset of the disease.
authors.affiliation: Service of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Emilie
authors.initials: E
authors.lastname: Jaquiéry
authors.forename: Samantha
authors.initials: S
authors.lastname: Jilek
authors.forename: Myriam
authors.initials: M
authors.lastname: Schluep
authors.forename: Pascal
authors.initials: P
authors.lastname: Meylan
authors.forename: Andreas
authors.initials: A
authors.lastname: Lysandropoulos
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pantaleo
authors.forename: Renaud A
authors.initials: RA
authors.lastname: Du Pasquier
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood / Q000134:cerebrospinal fluid*; D000956:Antigens, Viral / Q000276:immunology; D036022:Capsid Proteins / Q000276:immunology; D002469:Cell Separation; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000276:immunology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000134:cerebrospinal fluid; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid* / Q000821:virology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; C041788:Epstein-Barr viral capsid antigen; D007074:Immunoglobulin G; C417029:EBV-encoded nuclear antigen 1