Epstein-Barr Virus (EBV) has long been suspected of playing a role in the development of MS, and now the results from one large-scale study implicate EBV as a contributory cause of MS.
Researchers from the Harvard School of Public Health, Walter Reed Army Institute of Research, and a team of collaborators have observed for the first time that the risk of developing MS increases substantially following infection with EBV. The study appears in an advance online edition of the journal Annals of Neurology and will appear in a later print edition.
Hundreds of thousands of individuals not infected with EBV were followed up for several years through repeated blood samples collections. Researchers were then able to determine the time when individuals developed an EBV infection and its relation to MS onset.
"The recruitment of individuals before they were infected with EBV and following up with them for several years is the critical methodological aspect that makes this study qualitatively different from all previous work," said Alberto Ascherio, senior author of the study and professor of epidemiology and nutrition at Harvard School of Public Health and professor of medicine at Harvard Medical School.
EBV is a herpes virus and one of the most common human viruses worldwide. Infection in early childhood is common and usually asymptomatic. Late age at infection, however, often causes infectious mononucleosis. In the U.S., upwards of 95 percent of adults are infected with the virus, but free of symptoms. EBV has been associated with some types of cancer and can cause serious complications when the immune system is suppressed, for example, in transplant recipients. There is no effective treatment for EBV.
This is the first study based on the longitudinal follow-up of several thousand individuals who were not infected with EBV at the time of recruitment. The study population was made up of active-duty US Army, Navy, and Marines personnel who have at least one blood sample in the Department of Defense Serum Repository. The electronic databases of the Physical Disability Agencies of the US Army and Navy were then searched for individuals whose records indicated a possible diagnosis of MS reported between 1992 and 2004.
The researchers selected 305 individuals diagnosed with MS and who had blood specimens collected before the date of their diagnosis. Two controls for each case were then selected from the serum database and matched by branch of service, sex, date of blood collection, and age at time of blood collection.
The study found that MS risk is extremely low among individuals not infected with EBV, but it increases sharply in the same individuals following EBV infection.
"The observation that MS occurred only after EBV is a big step forward," said Alberto Ascherio. "Until now we knew that virtually all MS patients are infected with EBV, but we could not exclude two non-causal explanations for this finding: that EBV infection is a consequence rather than a cause of MS, and that individuals who are EBV negative could be genetically resistant to MS. Both of these explanations are inconsistent with the present findings," said Ascherio.
The study was supported by a grant from the National Institute of Neurological Disorders and Stroke.