Intrathecal immune responses to EBV in early MS.
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.
Jaquiéry
Emilie
E
Service of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Jilek
Samantha
S
Schluep
Myriam
M
Meylan
Pascal
P
Lysandropoulos
Andreas
A
Pantaleo
Giuseppe
G
Du Pasquier
Renaud A
RA
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
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