Intrathecal immune responses to EBV in early MS

• Published in: European journal of immunology 2010-03, Vol.40 (3), p.878-887
• Main Authors: Jaquiéry, Emilie, Jilek, Samantha, Schluep, Myriam, Meylan, Pascal, Lysandropoulos, Andreas, Pantaleo, Giuseppe, Du Pasquier, Renaud A
• Format: Article
• Language: English
• Subjects: Adult; Antibodies, Viral - blood; Antibodies, Viral - cerebrospinal fluid; Antigens, Viral - immunology; Capsid Proteins - immunology; Cell Separation; Cellular immune response; Cerebrospinal fluid; EBV; Epstein-Barr Virus Infections - complications; Epstein-Barr Virus Infections - immunology; Epstein-Barr Virus Nuclear Antigens - immunology; Flow Cytometry; Herpesvirus 4, Human - immunology; Humans; Humoral immune response; Immunoglobulin G - blood; Immunoglobulin G - cerebrospinal fluid; Multiple Sclerosis - blood; Multiple Sclerosis - cerebrospinal fluid; Multiple Sclerosis - virology; T-Lymphocytes, Cytotoxic - immunology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200939761

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.