EBV reactivation priming of the peripheral immune system in multiple sclerosis relapse [CD19+ B cell bulk RNA-seq]

Here, in this observational study of longitudinal blood samples from patients with relapsing-remitting MS, we used single-cell RNA sequencing, bulk transcriptomics, multiparameter flow cytometry and targeted viral reverse transcription quantitative polymerase chain reaction (RT−qPCR) to construct a time-resolved atlas of immune perturbations surrounding relapse.

A reproducible pre-relapse signature in monocytes and B cells, emerging up to 3 months before clinical onset, was enriched for host genes responsive to Epstein−Barr virus (EBV) lytic reactivation factors. RT−qPCR confirmed elevated EBV LMP-1 transcripts in pre-relapse B cells, and flow cytometry demonstrated expansion of CD11c+ atypical B cell populations displaying EBV surface protein gp350. Pre-relapse transcriptional modules overlapped with MS genome-wide association study (GWAS) risk loci and EBNA-2-bound enhancers, suggesting that inherited MS susceptibility and EBV-responsive programs operate through shared regulatory elements.