Intrathecal immune responses to EBV in early MS

Eur J Immunol. 2010 Mar;40(3):878-87. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral / blood
  • Antibodies, Viral / cerebrospinal fluid*
  • Antigens, Viral / immunology
  • Capsid Proteins / immunology
  • Cell Separation
  • Epstein-Barr Virus Infections / complications*
  • Epstein-Barr Virus Infections / immunology*
  • Epstein-Barr Virus Nuclear Antigens / immunology
  • Flow Cytometry
  • Herpesvirus 4, Human / immunology
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / cerebrospinal fluid
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / cerebrospinal fluid*
  • Multiple Sclerosis / virology*
  • T-Lymphocytes, Cytotoxic / immunology


  • Antibodies, Viral
  • Antigens, Viral
  • Capsid Proteins
  • Epstein-Barr Virus Nuclear Antigens
  • Epstein-Barr viral capsid antigen
  • Immunoglobulin G
  • EBV-encoded nuclear antigen 1