Journal of the American Medical Association (JAMA)
By Elda Hauschildt
The relationship between Epstein-Barr virus (EBV) infection and the development of multiple sclerosis (MS) has been confirmed, according to data from the United States military.
A nested case-control study was conducted among 3 million US military personnel who had had blood samples collected and stored between 1988 and 2000. Investigators led by Dr. Lynn Levin of the Walter Reed Army Institute of Research in Washington, DC, explain that infection with EBV had been associated with increased risk of MS, but that the temporal relationship was unclear.
They determined whether antibodies to the virus are elevated before patients develop MS by measuring antibodies for 83 people granted temporary or permanent military disability because of MS and comparing the results with two controls for each case. Controls matched cases by age, sex, race/ethnicity and dates of blood collection.
Serum samples were sent to the laboratory in triplets containing a case and two matched controls in random order, without identifying case/control status. The average time between blood collection and MS onset was four years.
Indirect immunofluorescence was used to determine immunoglobulin G (IgG) and IgA antibodies to EBV viral capsid antigen (VCA) and anti-early antigen complex. Anti- complement immunofluorescence determined IgG antibodies against the EBV virus nuclear antigen (EBNA) complex and two of its individual members, EBNA-1 and EBNA-2.
The researchers also examined IgG antibody titres against cytomegalovirus (CMV) to assess the specificity of any association between MS and EBV serology.
Serum levels of IgG antibodies to VCA or EBNA complex proved to be the strongest predictors of MS. Compared with people in the lowest VCA category, those in the highest had a relative risk of 19.7. Relative risk in the highest category of EBNA complex titres compared with the lowest category was 33.9.
The investigators say similar strong positive associations between EBV antibodies and MS risk were already present in samples collected five or more years before patients developed MS.
They comment: "Although the date of onset of MS is difficult to establish accurately, and many patients at the time of clinical onset have multiple silent MRI lesions, the lack of variation in our study in anti-EBV antibody titres between samples collected six to 11 years before the estimated MS onset and later samples suggests that the increased antibody response to EBV occurs early in relation to the pathological process that leads to demyelination and clinical disease."
No association was found between cytomegalovirus antibodies and MS.
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