Study illuminates the link between the Epstein-Barr virus and multiple sclerosis

A new study illuminates the connection between the Epstein-Barr virus (EBV) and multiple sclerosis (MS), pointing to a causal role for reactivation of the virus in triggering MS attacks in people with certain genetic risk factors. In a study of blood samples from more than 100 participants with MS, Mass General Brigham researchers detected increased EBV lytic activity in immune cells up to three months before MS relapse and discovered that these cells also showed elevated expression of genes linked to MS risk. The finding helps explain how a common virus and genetic risk may work together to trigger MS attacks. The work is published in Nature Medicine.

These findings open a whole new avenue for targeted therapeutics. Currently, most MS treatments work by broadly suppressing the immune system. Our results suggest there's an opportunity to be more precise and develop approaches that target EBV or the immune cells involved in relapse."

Tanuja Chitnis, MD, senior author, director of the Translational Neuroimmunology Research Center and Chief of the Division of Neuroimmunology, Mass General Brigham

Researchers analyzed blood samples from 114 patients with MS and 21 healthy participants in the Comprehensive Longitudinal Investigation of Multiple Sclerosis (CLIMB) study, a decades-long MS cohort based at Brigham and Women's Hospital, to track immune changes before relapse. The study included samples collected up to 90 days before participants experienced a relapse, allowing researchers to compare the pre-relapse immune state with periods of remission in the same patients.

To identify which immune cells changed the most before a relapse, researchers used single-cell RNA sequencing and other molecular techniques to analyze hundreds of thousands of immune cells. They found that B cells (immune cells that can house dormant EBV) showed some of the strongest changes, activating genes associated with antiviral responses, inflammation and EBV activity. The researchers also observed an increase of ABC-like B cells, a subset of cells linked to viral infections and autoimmune disease. They found that EBV proteins (derived from EBV genes) triggered MS risk genes to be expressed in immune cells prior to relapse, but not during remission or in healthy controls.

If these findings are validated in larger, prospective studies, blood biomarkers of EBV activity could help identify patients at increased risk of relapse, complementing MRI scans and existing blood biomarkers that typically detect disease activity only after inflammation is already underway. The authors note that future studies are needed to determine whether these findings extend to early-stage and progressive forms of MS.

"We believe this work provides foundational insights into the cause of multiple sclerosis," said Chitnis. "This study puts all the pieces together, showing a timeline of how the reactivated virus interacts with risk genes to unleash inflammation before relapse occurs."