An altered immune response to Epstein-Barr virus in multiple sclerosis: a prospective study.
OBJECTIVE
To investigate the association between human herpesviruses and multiple sclerosis (MS), as well as between measles virus and MS.


METHODS
The authors identified prospectively collected serum samples from 73 MS cases and retrospective sera from 161 MS cases in two population-based serum bank registers. Analyses of IgG antibody responses in cases and matched referents were performed for Epstein-Barr virus (EBV [EBNA-1 and VCA]), human herpesvirus 6 (HHV-6), herpes simplex virus (HSV), varicella zoster virus (VZV), and measles.


RESULTS
All cases showed signs of past EBV infection. High activity to EBNA-1 and HHV-6 significantly (borderline significance for HHV-6) increased the risk for MS in prospective sera. A discrepancy between activities to EBNA-1 and VCA was striking in MS samples collected less than 5 years before relapsing-remitting MS onset, where high activity to EBNA-1 significantly increased, and high VCA activity significantly decreased the risk for MS. There was no support for major causal roles for HSV, VZV, or measles.


CONCLUSIONS
Individuals who will develop MS exhibit an altered immune response against the EBV virus characterized by a high IgG activity to EBNA-1 in the absence of high activity to VCA, this being most pronounced in the 5-year period preceding MS onset.
Sundström
P
P
Department of Neurology, Umeå University Hospital, Sweden. peter.sundstrom@neuro.umu.se
Juto
P
P
Wadell
G
G
Hallmans
G
G
Svenningsson
A
A
Nyström
L
L
Dillner
J
J
Forsgren
L
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000276:immunology; D036022:Capsid Proteins / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology* / Q000821:virology*; D011446:Prospective Studies; D012189:Retrospective Studies
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