Research Suggests Epstein-Barr Virus Cause Increases Risk of Multiple Sclerosis

The 2022 study shows "compelling evidence" that EBV is the leading trigger of multiple sclerosis, but experts stress that other environmental and genetic factors also matter.

Multiple sclerosis, like many autoimmune diseases, is characterized by chronic inflammation—it's the work of the body's own immune system, attacking what it's meant to protect. In the case of MS, the body attacks its myelin sheath, a protective covering for the nerves in the brain and spinal cord.

Researchers have struggled for years to figure out what triggers a body with MS to turn on itself. Now, they've found the most compelling evidence to date that it could be a common infection, specifically one caused by the Epstein-Barr virus (EBV).

The findings come from a study, published in January 2022 in the journal Science. Though the researchers recognized that EBV is not the only risk factor for MS, they said the study still suggests that EBV is the leading cause of MS. Here, experts in the field of MS help parse out this new research, and explain what the findings mean for your health right now—and possibly in the future.

EBV and MS connection
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What Does the New Study Say About EBV's Link to MS?

Though researchers have previously suspected that EBV is a top risk factor for developing MS, causality—meaning that an EBV infection can directly cause MS—has been hard to study, since a randomized controlled trial is out of the question (you can't purposefully infect some people with EBV to see which ones end up developing MS). The group of scientists in this study, led by Harvard T.H. Chan School of Public Health researchers, got around this issue by conducting an "experiment of nature" in which they watched scenarios play out naturally in a longitudinal investigation.

In collaboration with the US Military, the research team examined data—collected from serum samples—from more than 10 million people on active duty in the US Armed Forces collected between 1993 and 2013. The samples, left over from HIV blood tests performed biennially on active-duty service members, were used to identify EBV status and the relation between EBV infection and MS onset.

Of the 10 million active-duty members, researchers identified 955 cases of MS, but only 801 of those cases had serum samples available to assess EBV status. All but one of those 801 MS cases tested positive for EBV antibodies at the time of MS onset, meaning they had previously had the infection.

Overall, the risk of MS increased 32-fold after an EBV infection but remained unchanged after contracting other viruses like cytomegalovirus (CMV). Researchers also found that there was about a five-year gap between the first EBV-positive serum sample to the onset of MS.

Study authors say these findings cannot be explained by any other known risk factor, and suggest that EBV is the leading cause of MS. "The hypothesis that EBV causes MS has been investigated by our group and others for several years," Alberto Ascherio, MD, DrPH, professor of epidemiology and nutrition at Harvard Chan School and senior author of the study, said in a press release. "But this is the first study providing compelling evidence of causality."

Does This Mean if You've Had EBV, You'll Get MS?

No, it just means that if you've had EBV—which is something you may or may not be aware of; sometimes it can cause infectious mononucleosis, other times it can feel like a brief cold- or flu-like illness—you may have a higher risk of developing MS, compared to someone who hasn't had EBV.

In a perspective piece also published in Science, two professors from Stanford University's Department of Medicine—William H. Robinson, MD, PhD; and Lawrence Steinman, MD—explained that nearly everyone is infected with EBV at some point, but only a small fraction of them go on to develop MS. That means other risk factors must be present in order for the development of MS.

"A mixture of environmental triggers in a genetically susceptible host is what likely leads to the disease," Claire S. Riley, MD, assistant professor of neurology at Columbia University Medical Center and clinical director of the Multiple Sclerosis Center, tells Health. According to Dr. Riley, who was not involved in the study, those environmental factors include low vitamin D levels, obesity, and cigarette smoking. Genetics also play a key role in the development of MS; Dr. Riley adds that researchers have found about 100 genes that may contribute to a person's risk.

Still, Dr. Riley says the results of this study provide the most convincing evidence researchers have seen so far that EBV could trigger multiple sclerosis—and that information could go on to prevent both EBV and potentially MS in the future.

What’s the real benefit of this study for the general public?

Currently, there's no vaccine available to help prevent EBV—but this study adds to evidence that one may be increasingly necessary.

"The conversation is shifting from 'how can we reduce risk of MS in the population?' to 'How can we prevent MS from occurring in the first place?'" Kassandra L. Munger, ScD, MS project director at the Harvard T. H. Chan School of Public Health and one of the study authors, tells Health. "I think this opens up avenues in other areas because EBV can contribute to other diseases as well, [and] an EBV vaccine may not only prevent MS but also other conditions, so I think there's a lot of promise."

To that end, an EBV vaccine is already in the works: Moderna announced on January 2022 that they had begun clinical trials for their mRNA EBV vaccine—the same type of technology used to create the COVID-19 vaccines. One person has been dosed with the vaccine so far, but Moderna plans to enroll approximately 270 participants between the ages of 18 and 30, with the hope that the vaccine will prevent EBV-induced infectious mononucleosis, and potentially EBV infection.

An EBV vaccine could serve as a primary preventative strategy, and Dr. Riley says that the idea of giving it to kids and young adults at risk of developing EBV and potentially preventing that environmental trigger is appealing. Understanding the relationship between EBV and multiple sclerosis may also help with public awareness of why kids might be offered another vaccine in the future.

While an EBV vaccine may help prevent multiple sclerosis in the future, it may not help people currently living with the disease. But according to Martin I. Belkin, DO, a neurologist and medical director of the Michigan Institute for Neurological Disorders' Multiple Sclerosis Center who was not involved in the study, these results may also shape future multiple sclerosis therapies by focusing on treatments that target EBV infection or immune cells infected with EBV.

"I think there's a reason for great hope for the future of patients with MS and reducing the incidence of MS overall in our population," Dr. Belkin says.

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