Mar 05, 2009
New Studies Bolster Possible Link Between Epstein-Barr Virus and MS
Summary: Researchers at the University of Buffalo, New York report two studies that add to growing findings linking the Epstein-Barr virus (EBV) with multiple sclerosis. One study suggests a link between EBV exposure and the loss of nerve tissue, while the other explores interactions between a person’s genes and EBV. Robert Zivadinov, MD, PhD, and colleagues at the University of Buffalo collaborated with researchers at the University of Trieste, Italy for a study reported in The Journal of Neurology, Neurosurgery, and Psychiatry (2009 Jan 23, Epub ahead of print) and the Buffalo group reports other findings in Journal of Neuroimmunology (2009 Feb 14, Epub ahead of print).
Background: Epstein-Barr virus (EBV) is a herpesvirus known to cause infectious mononucleosis and other disorders. Most people in the general population have antibodies in their blood showing that they have been exposed to the virus. After an initial infection EBV becomes latent or dormant, and can subsequently be reactivated. EBV infects B cells, the cells of the immune system that make antibodies. 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.
Several previous studies have suggested a possible link between EBV and MS, and studies suggest that people who have had infectious mononucleosis have double the normal risk of developing MS; but other infectious agents have also been linked to MS, and there is no direct evidence that proves that EBV triggers MS. Some researchers suggest that the way the immune system responds to infections, rather than the infectious agent itself, may lead to the onset of MS. Investigators recently reported finding traces of Epstein-Barr virus in postmortem brains examined from people with different forms of MS. They found the traces of EBV infection in immune cells (B cells and plasma cells) that had infiltrated the brain.
EBV-MRI Study: In this study, 135 people with MS were evaluated as part of a large-scale genetics/epidemiology project at the MS Center at the University of Trieste, Italy. Participants were between the ages of 18 and 70. People were excluded if they were in the midst of an MS relapse, if they had taken steroids or had had viral infections in the preceding three months, or if they had had a cold in the preceding month. The study group was not compared to a control population. Levels of immune system antibodies against EBV were measured, and participants underwent brain MRI scans within one month after blood samples were drawn to test for EBV antibodies. In a subset of 50 participants, EBV measurements and MRI scans were available from a different study that had been performed three years earlier, allowing investigators to observe differences over time.
In this study, people who had higher blood levels of EBV antibodies tended to have lower values of gray matter fraction and brain parenchymal fraction – two MRI measures whose decrease indicates loss of nerve tissue volume. Among the subgroup for whom earlier data were available, higher levels of EBV antibodies were associated with more brain tissue loss, as measured by brain parenchymal fraction three years later. These findings suggest a possible link between nerve tissue loss and antibodies to EBV.
Study of EBV and Genes: In a second study by the Buffalo researchers, they sought to establish a role for the interactions between a person’s genes and an environmental factor, in this case EBV. A group of 93 people with MS and 122 healthy controls were tested for antibodies against EBV as well as the pattern of specific immune function genes, called HLA genes, that have been associated with susceptibility to MS in some people. Participants underwent MRI scans and were assessed for brain parenchymal fraction as an indicator of brain tissue loss.
In this study, levels of EBV antibodies in the blood of people with MS and controls were similar. The presence of the HLA B7 gene was significantly associated with higher MRI lesion volumes, but although there were trends toward increased EBV antibody levels in people with this gene, the association was not statistically significant. By contrast, the gene HLA A2, which some studies have shown may reduce a person’s risk for MS, was associated with lower MS disability (as measured by the EDSS scale) and a trend toward decreased EBV antibody levels.
“These studies are interesting because they add to a growing body of data related to the possible link of EBV to MS, but also because they begin to address questions about how genes and an environmental factor like EBV may interact to influence the course of MS,”
commented John Richert, Executive Vice President of Research & Clinical Programs for the National MS Society.
Designing such studies – that confirm or invalidate a role for specific risk factors in the development of MS – was the subject of a recent workshop convened by the Society. Read a summary of this event.