Stronger evidence found linking Epstein-Barr virus and risk of multiple sclerosis

Boston, MA Researchers from the Harvard School of Public Health, Kaiser Permanente, and a team of collaborators have found further evidence implicating the Epstein-Barr virus (EBV) as a possible contributory cause to multiple sclerosis (MS). The study appears in the advance online edition of the June 2006 issue of Archives of Neurology.

MS is a chronic degenerative disease of the central nervous system. Women are more likely than men to get the disease and it is the most common neurologically disabling disease in young adults. Although genetic predisposition plays an important role in determining susceptibility, past studies have shown that environmental factors are equally important.

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% 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.

The study population was made up of more than 100,000 members of the Kaiser Permanente Northern California (KPNC) health plan, who provided blood specimens as part of medical examinations between 1965 and 1974. The KPNC maintained the medical records of all its members, including those who provided specimens, in electronic databases. Between 1995 and 1999, those databases were searched for evidence that would indicate a possible diagnosis of MS.

The researchers selected 42 individuals diagnosed with MS and that had serum specimens collected before the date of diagnosis. Two controls for each case were then selected from the serum database and matched by sex, date of blood collection, and age at time of blood collection.

The study's main finding was that antibodies--proteins produced by the body to fight infection--to the Epstein-Barr nuclear antigen (EBNA) complex and its component EBNA-1 in individuals with MS were elevated up to 20 years before the first symptoms of the disease and persisted thereafter. Lead author Gerald N. DeLorenze, Ph.D., Kaiser Permanente Division of Research, and his colleagues cite three other studies--the Nurses' Health Study, a U.S. army personnel study, and a study in Vasterbotten County, northern Sweden--that also showed a similar finding, but none of the previous studies could draw data from blood samples collected two decades or longer before the onset of MS symptoms.

"Collectively, the results of this and the previous studies provide compelling evidence that infection with EBV is a risk factor in the development of MS," said Alberto Ascherio, senior author of the study and Associate Professor of Nutrition and Epidemiology at Harvard School of Public Health.

Although there is strong evidence of an association between EBV and MS risk, researchers are still uncertain how the Epstein-Barr virus contributes to the inflammation of the myelin--the protective coating around the nerve fibers--that leads to the debilitating disease. The fact that EBV infects B-lymphocytes, cells of the immune system that are part of our defenses against infection, seems to fit with the evidence of immune dysfunction in MS, but rigorous work remains to be done to unravel the molecular mechanisms.

The authors note that the mounting evidence that relates EBV infection to other autoimmune diseases, particularly systemic lupus, suggests that EBV may have a broad role in predisposing genetically susceptible individuals to autoimmune reactions and that comparative studies of EBV, MS, and lupus could be useful to find new clues to their possible commonalities.

"Discovering strong risk factors is the task of epidemiologists and an important initial step in finding ways to diagnose, treat, and prevent MS," said Ascherio. "A focused multidisciplinary effort is now needed to complete the puzzle and thus open the door to new therapeutic approaches."

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The study was supported by a grant from the National Institute of Neurological Disorders and Stroke and by a pilot grant from the National Multiple Sclerosis Society. Harvard School of Public Health is dedicated to advancing the public's health through learning, discovery, and communication. More than 300 faculty members are engaged in teaching and training the 900-plus student body in a broad spectrum of disciplines crucial to the health and well being of individuals and populations around the world. Programs and projects range from the molecular biology of AIDS vaccines to the epidemiology of cancer; from risk analysis to violence prevention; from maternal and children's health to quality of care measurement; from health care management to international health and human rights. For more information on the school visit: www.hsph.harvard.edu


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