Recent evidence supports Epstein-Barr virus as ‘leading cause’ of MS

SAN DIEGO — Evidence over the past 10 years supports the role of Epstein-Barr virus in the development of MS, according to a presenter at ACTRIMS 2023.

“The majority of primary [Epstein-Barr virus] infections in the world are in childhood and are subclinical,” Marianna Cortese, MD, PhD, of the Harvard T.H. Chan School of Public Health, said. “Later age of infection increases the risk for symptomatic infection and is related to better sanitary conditions and higher socioeconomic status.”

According to Cortese, 90% to 95% of the global adult population is infected with Epstein-Barr virus (EBV), which stands in “stark contrast” to the lifetime risk for developing MS, which is one in 200 in women and one in 400 in men.

Although EBV was considered for decades as a possible etiologic factor for MS, evidence for causality was inconclusive, Cortese said, as the “gold standard” of conducting a randomized clinical trial was not possible. Ideally, researchers would like to identify a group of individuals not infected with EBV and monitor them over time for development MS. That remains challenging, she said, due to the high prevalence of EBV and relative rarity of MS.

However, a recent study by Cortese and colleagues revealed the “most compelling evidence to date” of EBV infection as a leading cause of MS. Researchers analyzed more than 62 million serum samples from 10 million United States military personnel and identified 955 MS patients who were matched by sex, age, race, ethnicity, date of blood collection and military branch with 1,843 controls. At baseline, 35 MS cases and 107 controls were EBV-negative.

According to Cortese, questions of a reverse causality between EBV and MS could be answered by measuring neurofilament light chain levels as well antibody titers against the human virome. She also noted that research findings could not be explained by factors linked to MS, such as family history, vitamin D deficiencies, smoking or early-onset of obesity.

“Evidence supporting the role of EBV in MS etiology has been converging in the last decade,” Cortese said.

Reference:

• Bjornevik K, et al. Science. 2022;doi:10.1126/science.abj8222.