A Causal Link Between Epstein-Barr Virus and Multiple Sclerosis
Post by Negar Mazloum-Farzaghi
The takeaway
To investigate the cause of multiple sclerosis, researchers examined data from over 10 million US military recruits. Examination of blood samples provided strong evidence that Epstein-Barr virus is linked to multiple sclerosis.
What's the science?
Multiple sclerosis (MS) is a chronic neurodegenerative disease of the central nervous system that attacks the nerve fibers and myelin sheathing of the brain and spinal cord. While the cause of MS is currently unknown, previous evidence has pointed to viral infection with Epstein- Barr virus (EBV) as a potential trigger of MS. EBV is one of the most common human viruses that can give rise to infectious mononucleosis and can persist in latent form throughout the life of the host. Evidence of causality between EBV and MS remains to be investigated.
This week in Science, Bjornevik and colleagues examined a cohort of over 10 million young adults in the US military, 955 of whom were diagnosed with MS over a 20-year period, to test the hypothesis that there is a causal link between EBV and MS.
How did they do it?
In order to investigate the relationship between EBV and MS, the authors collaborated with the US military to examine blood samples of more than 10 million racially diverse individuals who were serving in the US military over the span of 20-years. The US military screens for HIV at the start of service and biennially thereafter, and residual serum from these tests are archived in a repository. Using the archived serum, the authors determined EBV status at the time of the first sample and the association between EBV infection and MS development during active military duty. They found that 5.3% of individuals were negative for the EBV virus at the time of first sample.
In total, 955 MS cases were documented among active-duty military personnel. For each MS case, evidence for EBV infection was assessed by examining three serum samples which were collected before the start of MS onset (the first collected sample, the last collected sample prior to disease onset, and one sample in between). Next, the MS cases were matched (for age, sex, and race) to two randomly selected individuals without MS. There were 801 individuals with MS and 1566 control individuals with samples available to assess EBV infection status. Most individuals in the study were 20 years of age or younger at the time of their first blood sample, and those who developed MS had a symptom onset of a median of 10 years after the time of their first sample.
What did they find?
To investigate the risk of MS from EBV infection, the authors identified 35 MS cases and 107 controls who were EBV-negative in their initial collected blood sample. All but one of these 35 EBV-negative MS cases eventually tested positive for EBV antibodies, indicating that almost all MS cases were infected with EBV prior to MS symptom onset. Importantly, there were no cases of MS among individuals who remained EBV-negative. To assess whether other viruses were also associated with the MS cases, the authors investigated cytomegalovirus, a similar virus to EBV. They found that cytomegalovirus infection was not associated with an increased risk of MS.
The authors also investigated serum concentrations of neurofilament light chain (sNfL), a biomarker of neuroaxonal degeneration in the samples of MS cases and controls who were EBV-negative at baseline. They found that sNfL levels in EBV-negative individuals at baseline who eventually went on to develop MS were similar to control levels before the time of EBV infection in those who went on to develop MS. However, sNfL levels increased after EBV infection. Thus, there was no indication of neuroaxonal degeneration before EBV infection in individuals who later developed MS, suggesting that EBV infection preceded MS pathological onset.
What's the impact?
This study provides the strongest evidence to date that EBV infection can lead to MS. Future research should investigate the underlying biological mechanisms involved in the relationship between EBV and MS, which could ultimately lead to the development of interventions, such as vaccination, to prevent MS before onset.
