Epstein-Barr virus may be ‘initial trigger’ of MS

Epstein-Barr virus infection, which causes mononucleosis, may represent a primary cause of MS, according to results of a longitudinal analysis published in Science.

“Causality implies that some individuals who developed MS after EBV infection would not have developed MS if they had not been infected with EBV,” Kjetil Bjornevik, MD, of the department of nutrition at Harvard T. H. Chan School of Public Health, and colleagues wrote. “Ruling out a randomized trial, the gold standard to study this counterfactual occurrence is an ‘experiment of nature,’ a longitudinal investigation of MS incidence in a cohort of EBV-negative individuals, some of whom will be infected with EBV during the follow-up and some who will not. The ubiquitous nature of EBV, which infects [approximately] 95% of adults, and the fact that MS is a relatively rare disease, has until now impeded such an investigation.”

Investigators examined the role of EBV in MS among a cohort of more than 10 million young adults who were actively serving in the U.S. military. Of these, 955 received an MS diagnosis during their service period. Bjornevik and colleagues analyzed up to three serum samples, provided by the Department of Defense Serum Repository, from each individual with MS; samples were collected before the onset date of MS. The investigators then matched these individuals to two randomly selected individuals who did not have MS, based on having the same age, sex, race/ethnicity, military service branch and dates of blood sample collection.

Results showed MS risk increased 32-fold following EBV infection; however, MS risk did not increase following infection with other viruses, including cytomegalovirus. Further, neurofilament light chain serum levels, which serve as a biomarker of neuroaxonal degeneration, increased only after EBV seroconversion.

According to Bjornevik and colleagues, known MS factors cannot explain these findings, suggesting EBV may be the leading cause of MS.

“One of the most effective treatments for MS is anti-CD20 monoclonal antibodies, which deplete circulating memory B cells, the primary site of persistent latent EBV infection,” the researchers wrote. “This, and preliminary results obtained with EBV-specific T cell therapy, suggest that EBV, in addition to causing MS, contributes to MS clinical course, which could thus be potentially modified by antivirals. Directly targeting EBV could have major advantages compared with anti-CD20–based therapies, which have to be administered by intravenous infusion and may increase the risk of infections.”

In a related editorial, William H. Robinson, MD, PhD, professor of immunology and rheumatology, and Lawrence Steinman, MD, professor of neurology and neurological sciences, both in the department of medicine at Stanford University, outlined novel possibilities for MS interventions.

“There may be new opportunities for therapy: Would a vaccine against EBV protect against MS? Can the B cells that dwell in the CSF be killed or inactivated with therapeutics? Would antivirals that target EBV provide effective therapy, especially when given early in the course of disease?

“Now that the initial trigger for MS has been identified, perhaps MS could be eradicated,” they added.