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Study Provides Strongest Evidence Yet for the Role of Epstein-Barr Virus in Triggering Multiple Sclerosis

January 13, 2022

Researchers at Harvard and their collaborators report on a study published in Science that provides the strongest evidence to date that the Epstein-Barr virus (EBV) is a trigger for multiple sclerosis. This study does not address the question of whether EBV is involved in ongoing disease activity in people who already have MS.
 
Taking advantage of a series of blood samples from more than 10 million military personnel, the research team demonstrated that EBV infection precedes both the symptoms of MS and nervous system damage, and that becoming infected significantly increases the risk for developing MS in susceptible individuals (people whose genetic background, environment, and lifestyle increases their risk for getting MS).
 
“This is an impressive study from a highly regarded research group that strengthens the scientific consensus that infection with Epstein-Barr virus is a trigger for MS,” noted Dr. Bruce Bebo, Executive Vice President of Research for the National MS Society. “Development of Epstein-Barr virus vaccines is underway, and once one is proven safe and effective, it should be tested with haste in people at high risk for MS.”
 
The National MS Society invested in this study as part of its ongoing research commitment to ending MS.
 
(See Key Points Below)
 
Background
  • EBV: The Epstein-Barr virus is spread primarily through contact with infected saliva. It is very common, and most people are infected by it, generally without harm, in childhood. In adolescence and adulthood, it can cause infectious mononucleosis, a disease that increases the risk of later developing MS. The virus stays in the body throughout a person’s lifetime, and has been linked to certain cancers and autoimmune diseases. There is currently no treatment that can eliminate the virus from a person’s system.
  • Causes of MS: MS is thought to be caused by a combination of factors, including an individual’s genetic background, gender, environment, and lifestyle. To date, researchers have not been able to identify a single virus as the trigger for MS. Several viruses have been studied, with Epstein-Barr virus showing the most evidence thus far, but multiple steps are required to show that a particular virus is an actual cause of MS. Researchers must prove that: the virus is in the body before MS develops, and that the virus causes the disease and is not just happening alongside the disease.
 
Details of the Study
  • The Harvard team used blood samples collected to test for HIV among more than 10 million active-duty United States military personnel between 1993 and 2013. Looking for specific antibodies that signal past infection, they determined the EBV status at the time the first sample was taken, and then followed additional samples to determine the relation between EBV infection and MS onset during the period of active duty. The team identified 801 people who developed MS and 1,566 controls without MS whose samples were available.
  • The results show that in the first blood samples taken, only 35 of the people who developed MS and 107 of controls were negative for EBV infection. Tracking their samples over time, the team found that the risk of developing MS increased 32 times in those who became positive for EBV infection. All infections occurred before MS onset. In the follow up samples, all but one person with MS became infected.
  • The team then sought to rule out other possibilities. They tested for an immune response to cytomegalovirus (which is transmitted via saliva similarly to EBV), but this virus was not linked to an increase in MS risk. Using a novel tool called VirScan, which screens for evidence of an immune response to approximately 200 viruses, they also found no links between other viruses and MS risk. This indicates that heightened MS-related immune activity was not the source of the team’s EBV findings.
  • To test whether EBV infection predated MS-related nervous system damage, the team looked at levels of a molecule called neurofilament light chain (NfL), which is a substance released into the spinal fluid and blood when nerve wires (axons) are damaged. Studies have linked it to MS relapses and progression. In people with MS who were EBV negative at the beginning of the study, there was no indication of elevated NfL until they were infected with EBV. After infection, elevated levels were detected prior to the MS diagnosis.
 
“Longitudinal analysis reveals high prevalence of Epstein-Barr Virus associated with multiple sclerosis,” by Kjetil Bjornevik, Marianna Cortese, Brian C. Healy, Jens Kuhle, Michael J. Mina, Yumei Leng, Stephen J. Elledge, David W. Niebuhr, Ann I. Scher, Kassandra L. Munger, and Alberto Ascherio, was published in Science on January 13, 2022.
 
Key Points
  • The Epstein-Barr virus is a leading trigger of MS, but it does not act alone. Research suggests that MS is caused by a combination of genetic and environmental factors, and so this virus is not likely to act alone, but may trigger MS in susceptible individuals. 
  • We don’t know yet if the Epstein-Barr virus causes relapses or influences the MS disease course. However, having an anti-viral medicine that combats the virus may help answer that important question. At least one study is testing an experimental anti-EBV medication in people with MS, and there are several experimental EBV vaccines in development, including this recent one announced by Moderna testing its safety in healthy volunteers. 
  • Currently, there is no way to avoid infection by the Epstein-Barr virus. The Epstein-Barr virus is easily passed between people and most people have already been exposed. There are vaccines in development that, if proven safe and effective, should be tested in people who are at higher risk for MS, such as people with close family members with MS. 
  • It is possible in the future an EBV vaccine could prevent MS. We know that this virus does not act alone, but rather in combination with other risk factors such as a person’s genes and environment. In addition to the possibility of an EBV vaccine, researchers are working on ways to calibrate any individual’s personal risk for developing MS to provide a possible rationale for intervening before it takes hold.

About Multiple Sclerosis

Multiple sclerosis is an unpredictable, often disabling disease of the central nervous system. Symptoms range from numbness and tingling to blindness and paralysis, and there is currently no cure for MS. The progress, severity and specific symptoms of MS in any one person cannot yet be predicted, but advances in research and treatment are leading to better understanding and moving us closer to a world free of MS. An estimated 1 million people live with MS in the United States. Most people with MS are diagnosed between the ages of 20 and 50, and it affects women three times more than men.

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