Two New Studies Link Epstein-Barr Virus to Risk of Developing MS
Posted Mar 21 2010 7:20am
Mar 16, 2010
Two new studies are adding to an increasing body of evidence that shows a possible role for Epstein-Barr virus (EBV) in the development of MS. Alberto Ascherio, MD, DrPH (Harvard School of Public Health, Boston) and colleagues showed that an EBV-positive blood test preceded MS diagnosis in a large sample of MS cases identified through U.S. military databases. ( Annals of Neurology, accepted online January 20, 2010 ) Manuel Comabella, MD (Hospital Universitari Vall d’Hebron, Barcelona) and an international team of colleagues report that reactions to a specific protein associated with EBV were increased in people with MS compared with siblings who did not have MS ( Multiple Sclerosis 2010;16:355–358 )
Background on EBV and MS: The cause of MS, an unpredictable immune-mediated disease that attacks the central nervous system, is unknown, but the disease is thought to occur when susceptible individuals encounter a triggering factor or factors in their environment. Epstein-Barr virus is a herpesvirus known to cause infectious mononucleosis and other disorders. Most people in the general population have been exposed to the virus. Several previous studies have suggested a possible link between EBV and MS, but other infectious agents have also been linked to MS, leading some researchers to suggest that the way the immune system responds to infections, rather than the infectious agent itself, may lead to the onset of MS.
Harvard Study: Dr. Ascherio and colleagues identified 305 cases of definite or probable MS in the electronic databases of the Physical Disability Agencies of the U.S. Army and U.S. Navy reported between 1992 and 2004, which had at least one blood sample collected prior to the date of MS onset. For each case, they obtained up to three blood samples (the earliest and latest available, as well as a third sample collected between those two). Two controls who did not have MS were chosen from the databases for each case.
At the start of the study, all of the 305 MS cases except for 10 (3.3%) and all of the 610 controls except for 32 (5.2%) had blood samples that tested positive for EBV. A positive blood test means that the individual’s immune system had at some point been infected by the virus and mounted an immune response against it. All of the 10 initially EBV-negative cases became positive before the onset of MS, but only 10 (35.7%) of the 28 controls became positive. They found no significant association between another virus – cytomegalovirus – and MS risk. The authors conclude that MS risk is low in individuals who have not been infected with EBV, and increases significantly in those individuals following EBV infection.
“This study suggests that conversion to EBV-positive status increases the risk of being diagnosed with MS,” said Nicholas LaRocca, PhD, Vice President of Health Care Delivery and Policy for the National MS Society, who served on the planning committee of the Society’s 2009 International Workshop On MS Risk Factors And Frequency. Proving a “cause and effect” relationship between EBV and MS requires many research steps. One of these steps is to show that EBV precedes MS, and these authors have shown evidence for that. “Now, we need more studies to confirm this finding. If EBV is to be identified as an MS trigger, we also need to show – and this is the most difficult step – a causal connection.” More research in this area is ongoing.
Barcelona Study: If MS is triggered in susceptible individuals by exposure to a virus, then why do siblings brought up in the same household – and presumably exposed to many of the same strains of viruses and infections – differ in terms of their risk for developing MS? Taking one approach to this question, Dr. Comabella and colleagues evaluated the immune system response to various virus-related proteins – including EBV, cytomegalovirus, and measles – evident in blood samples from 25 people with MS, compared with 49 of their siblings who did not have MS.
The investigators found that siblings did not differ in terms of showing signs of having been infected with any of the viruses tested. The only marked difference they found was in the immune responses to EBNA1, a viral protein associated with EBV. These responses (IgG) were significantly increased in people with MS compared with their unaffected siblings. The authors conclude that further studies are needed to understand the mechanism by which immune responses to an EBV protein might contribute to MS.