Five Studies explore relationship between Epstein-Barr Virus and MS
or print this bulletin in its original format.
Medical Update Memo
March 23, 2010
Researchers from Canada, the United States the EU report on work exploring the relationship between the Epstein Barr virus (EBV) and Multiple Sclerosis.
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 herpes virus 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.
Association of Infectious Mononucleosis with Multiple Sclerosis
A Population-Based Study Neuroepidemiology. Vol. 32, No. 4, 2009
Canadian geneticist Dr. Dessa Sadovnick and colleagues report on a population based approach to the relationship between viral illness and MS. Genetic and environmental factors have important roles in multiple sclerosis (MS) susceptibility. Several studies have attempted to correlate exposure to viral illness with the subsequent development of MS. In a Canadian population-based cohort, researchers investigated the relationship between prior clinical infection or vaccination and the risk of MS.
Using the longitudinal Canadian database, 14,362 MS index cases and 7,671 spouse controls were asked about history of measles, mumps, rubella, varicella and infectious mononucleosis as well as details about vaccination with measles, mumps, rubella, hepatitis B and influenza vaccines. Comparisons were made between cases and spouse controls. Spouse controls and stratification by sex appear to correct for ascertainment bias because with a single exception no significant differences were found between cases and controls for all viral exposures and vaccinations. However, 699 cases and 165 controls reported a history of infectious mononucleosis (p < 0.001, corrected odds ratio 2.06, 95% confidence interval 1.71-2.48). Females were more aware of disease history than males (p < 0.001).
Dr. Sadovnick and colleagues concluded that the data further confirms a reporting distortion between males and females. Historically reported measles, mumps, rubella, varicella and vaccination for hepatitis B, influenza, measles, mumps and rubella are not associated with increased risk of MS later in life. A clinical history of infectious mononucleosis is conspicuously associated with increased MS susceptibility. These findings support studies implicating Epstein-Barr virus in MS disease susceptibility, but a co-association between MS susceptibility and clinically apparent infectious mononucleosis cannot be excluded.
Elevated Epstein-Barr virus-encoded antigen-1 immune responses predict conversion to multiple sclerosis. Ann Neurol. 2009 Oct 13;67(2):159-169
Currently available markers for developing MS after a first inflammatory-demyelinating episode of the central nervous system, and markers for disability progression are still far from satisfactory. The authors of this study found that the concentration, in peripheral blood, of a specific protein produced after an infection by the Epstein-Barr virus was higher in people who had experienced a first attack compared to controls. Moreover, they found that people with higher concentrations of this protein, related to EBV, had a higher risk of developing MS and experiencing a worse clinical outcome over the following years. Interestingly, the other proteins studied, related to EBV and other viruses, did not show this capacity. Therefore, the authors propose that this protein be considered as a possible marker for the development of the disease and for disability progression.
Primary infection with the Epstein-Barr virus and risk of multiple sclerosis Annals of Neurology, accepted online January 20, 2010
Dr. Ascherio from Harvard University 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. They looked at cases for the years 1992 to 2004, and reported on those 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.
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.
Antiviral immune response in patients with multiple sclerosis and healthy siblings Multiple Sclerosis 2010; 16(3): 355-358
In Barcelona, researchers asked, “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.
Absence of Epstein-Barr virus in the brains and CSF of patients with multiple sclerosis. Neurology. 2010 Mar 10
The Epstein-Barr virus (EBV) has been largely associated with the risk of MS. The authors of this study aimed to investigate whether the presence of a possible latent or active EBV infection in the central nervous system (CNS) of people with MS could be actually playing a role in the development of the disease. After studying active brain MS plaques and different types of immune cells located in the CNS of people with MS, the authors found no evidence of latent or active EBV infection. Nor did they find specific anti-EBV antibody response within the CNS of people with MS. More investigations are needed to link the results of this study with the considerable number of studies that associate EBV infection with an increased risk of MS.
National Research and Programs
Offert en français.
The Multiple Sclerosis Society of Canada is an independent, voluntary health
agency and does not approve, endorse or recommend any specific product or therapy,
but provides information to assist individuals in making their own decisions.