[I've appended the abstract but think the lay version is useful here also. Given the EBV involvement, I thought some might find it of interest]
Researchers Find Further Evidence Linking Epstein-Barr Virus, Risk of MS
BOSTON -- March 4, 2010 -- Researchers have observed for the first time that the risk of multiple sclerosis (MS) increases by many folds following infection with the Epstein-Barr virus (EBV). This finding implicates EBV as a contributory cause to multiple sclerosis. The study appears in an advance online edition of the journal Annals of Neurology and will appear in a later print edition.
Hundred 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 senior author Alberto Ascherio, MD, Harvard School of Public Health, and Harvard Medical School, Boston, Massachusetts.
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 1 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 Dr. Ascherio. "Until now we knew that virtually all MS patients are infected with EBV, but we could not exclude 2 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."
"The evidence is now sufficiently compelling to justify the allocation of more resources to the development of interventions targeting EBV infection, or the immune response to EBV infection, as these may contribute to MS prevention," he said.
SOURCE: Harvard School of Public Health
Annals of Neurology
Volume 9999 Issue 999A, Page NA
Published Online: 20 Jan 2010
Copyright C 2010 American Neurological Association
Primary infection with the epstein-barr virus and risk of multiple sclerosis
Lynn I. Levin, PhD, MPH 1, Kassandra L. Munger, ScD 2, Eilis J O'Reilly, ScD
2 3, Kerstin I Falk, PhD 4, Alberto Ascherio, MD, DrPH 2 3 5 *
1Department of Epidemiology, Division of Preventive Medicine, Walter Reed Army Institute of Research, Silver Spring, MD 20910-7500 2Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA 3Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA 4Department of Virology, Swedish Institute for Infectious Disease Control, and MTC, Karolinska Institute, Solna, Sweden 5Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School
email: Alberto Ascherio (firstname.lastname@example.org)
*Correspondence to Alberto Ascherio, Professor of Epidemiology and Nutrition, Harvard School of Public Health, 665 Huntington Ave, Building II, Room 335, Boston, MA 02115
To determine whether multiple sclerosis (MS) risk increases following primary infection with the Epstein-Barr virus (EBV), we conducted a nested case-control study including 305 individuals who developed MS and 610 matched controls selected among the over 8 million active-duty military personnel with serum stored in the Department of Defense Serum Repository.
Time of EBV infection was determined by measuring antibody titers in serial serum samples collected before MS onset among cases, and on matched dates among controls. Ten (3.3%) cases and 32 (5.2%) controls were initially EBV negative. All of the 10 EBV-negative cases became EBV positive before MS onset; in contrast, only 35.7 % (10) of the 28 controls with follow-up samples seroconverted (exact p value = 0.0008). We conclude that MS risk is extremely low among individuals not infected with EBV, but it increases sharply in the same individuals following EBV infection. Ann Neurol 2010.
Received: 14 October 2009; Revised: 8 December 2009; Accepted: 8 January 2010