Study Identifies Epstein-Barr Virus Infection as a Leading Cause of Multiple Sclerosis

A general graphic of bacteria and viruses.

By Sarah Marshall

Between 2007 and 2016, more than 2,000 active duty service members were diagnosed with multiple sclerosis – a chronic inflammatory disease of the central nervous system that results in significant clinical disability. The cause of this disease has been unknown – that is, until a group of USU researchers recently discovered that Epstein-Barr virus infection could be a primary cause.

Dr. Ann Scher sits at a desk.
Dr. Ann Scher, a USU faculty member, recently
collaborated on a study that found Epstein-Barr
virus could be a primary cause of multiple
sclerosis. (Courtesy photo)
The collaborative study, “Longitudinal analysis reveals high prevalence of Epstein-Barr Virus associated with multiple sclerosis,” was published Jan. 13 in Science. The team of researchers found that the risk of multiple sclerosis increased 32-fold specifically after infection with Epstein-Barr virus, known for causing mononucleosis, or “mono,” but not after infection with the similarly transmitted cytomegalovirus. Furthermore, they found that levels of neurofilament light chain, a biomarker of neurodegeneration, also increased after Epstein-Barr infection.

The study was a collaboration between USU, Harvard Medical School, Massachusetts General Hospital, the University of Basel in Switzerland, and Brigham and Women’s Hospital. The researchers tested a hypothesis that multiple sclerosis is caused by a dysfunction of the immune system that is triggered by a viral infection. The Epstein-Barr virus is believed to be a top candidate, but evidence linking infection with the Epstein-Barr virus to multiple sclerosis has been inconclusive.

The researchers tested this hypothesis in a cohort of more than 8 million young adults on active duty in the U.S. military, 955 of whom were diagnosed with multiple sclerosis during their period of service. For each individual with multiple sclerosis, the researchers identified up to three serum samples (from the Department of Defense Serum Repository) collected before their onset date of multiple sclerosis. These individuals were then matched to two randomly selected individuals without multiple sclerosis of the same age, sex, race/ethnicity, branch of military service, and dates of blood sample collection.

These findings cannot be explained by any known risk factor for multiple sclerosis, and the researchers identified Epstein-Barr virus as a leading cause of multiple sclerosis. These findings further suggest that risk of multiple sclerosis might theoretically be modified by antiviral medications that directly target Epstein-Barr virus.  

“Biomarker studies such as this are only practical in very large datasets due to the rarity of the condition studied and long latency between infection and development of disease. This study is an illustration of the enormous value of the Department of Defense Serum Repository and its benefit to the research community and the world,” said Dr. Ann Scher, professor of Preventive Medicine and Biostatistics at USU, one of the study’s authors.

Multiple Sclerosis: Among service members of the active and reserve components of the U.S. Armed Forces and among other beneficiaries of the Military Health System, 2007-2016. Multiple sclerosis (MS) is an immune-mediated inflammatory demyelinating disease of the central nervous system, affecting approximately 400,000 people in the U.S. and more than TWO MILLION people worldwide. The inflammatory demyelination and axonal injury that characterize MS result in significant clinical disability and economic burden. This study makes a useful contribution to the literature on temporal changes in the incidence of MS by sex and race/ethnicity. FINDINGS: 1. Between 2007 and 2016, a total of 2,031 active component service members received incident diagnoses of MS. 2. The overall unadjusted incidence rate was 14.9 cases per 100,000 p-yrs. 3. During the surveillance period, unadjusted annual incidence rates of MS decreased by 25.4%. 4. The highest overall incidence rates were observed among service members diagnosed after age 30 with rates peaking among those aged 40 years or older. Note: Annual incidence rates of MS were higher among female service members than male service members and decreased by 42.2% during the 10-year period. Also, the higher overall incidence of MS among non-Hispanic blacks was found among females, and to a lesser degree, among males. MEDIAN AGE AT MS-CASE DEFINING DIAGNOSIS: 1. Age 32 years among active component members. 2. Age 37 years among reserve/guard members. 3. Age 48 years among non-service member beneficiaries. COMMON MS SYMPTOMS: Numbness, tingling in limbs, visual loss, double vision, motor weakness, gait disturbance. Access the full report in MSMR Vol. 24 No. 8 August 2017 at Health.mil/MSMR.
A 2017 study looked at the prevalence of multiple sclerosis in the military. (Infographic source: Defense Health Agency)