A study published in Nature Medicine has identified a potential causal mechanism linking Epstein-Barr virus (EBV) reactivation to multiple sclerosis (MS) relapse, finding that increased viral activity in immune cells can be detected up to three months before a relapse occurs in people with certain genetic risk factors. The research was conducted by investigators at Mass General Brigham using blood samples from participants in a long-running MS cohort.
The study analysed blood samples from 114 patients with MS and 21 healthy participants enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis (CLIMB) study at Brigham and Women’s Hospital. Samples collected up to 90 days before a relapse were compared with samples taken during periods of remission in the same patients, allowing the researchers to map immune changes in the pre-relapse window.
Using single-cell RNA sequencing and additional molecular techniques across hundreds of thousands of immune cells, the team found that B cells, which can harbour dormant EBV, showed the greatest pre-relapse changes, including activation of genes associated with antiviral responses, inflammation, and EBV activity. An increase in ABC-like B cells, a subset associated with viral infections and autoimmune disease, was also observed. Critically, EBV proteins were found to trigger expression of MS risk genes in immune cells prior to relapse, a pattern not observed during remission or in healthy controls.
The findings suggest that EBV reactivation and genetic susceptibility may act together to initiate the inflammatory cascade preceding MS relapse. If validated in larger prospective studies, blood biomarkers of EBV activity could complement MRI and existing biomarkers by providing earlier signals of impending disease activity. The authors also propose that more targeted therapeutic approaches directed at EBV or the specific immune cells involved in relapse may be worth pursuing alongside current broad immunosuppressive treatments.
Source: King DA et al. EBV reactivation priming of the peripheral immune system in multiple sclerosis relapse. Nature Medicine (2026). DOI: 10.1038/s41591-026-04665-3
