A new study found distinct immune changes preceding multiple sclerosis relapse. The findings provide new insight into how Epstein-Barr virus reactivation may trigger an MS attack in people with genetic risk factors. 

In a study of blood samples from more than 100 participants with MS, scientists at Mass General Brigham detected increased EBV lytic activity in immune cells up to three months before MS relapse and discovered these cells also showed elevated expression of genes linked to MS risk. 

Researchers analyzed blood samples from 114 patients with MS and 21 healthy participants in the Comprehensive Longitudinal Investigation of Multiple Sclerosis 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 prerelapse 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 linked to 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.

The study was published in the journal Nature Medicine.