Altered immune landscape of cervical lymph nodes reveals EBV signature in multiple sclerosis, 2025, Joona Sarkkinen et al

Editor’s summary
Epstein-Barr virus (EBV) infection predisposes individuals to multiple sclerosis (MS). Adaptive immune responses to EBV occur in deep cervical lymph nodes (dcLNs), yet the immune landscape in dcLN from patients with MS (pwMS) is not well understood. Sarkkinen et al. profiled immune cells from dcLNs of pwMS using fine-needle aspirations. By combining single-cell RNA sequencing and cellular indexing of transcriptomes and epitopes by sequencing, they identify expansion of double-negative memory B cells enriched for a transcriptional profile that resembled a lytic EBV infection. Furthermore, fewer germinal center (GC) B cells and GC T follicular helper cells were detected in pwMS, and GC clonality was reduced. These findings provide insight into MS pathogenesis at the site of adaptive immune response to EBV.

Abstract
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, and Epstein-Barr virus (EBV) infection is a prerequisite for developing the disease. However, the pathogenic mechanisms that lead to MS remain to be determined.

Here, we characterized the immune landscape of deep cervical lymph nodes (dcLNs) in newly diagnosed untreated patients with MS (pwMS) using fine-needle aspirations. By combining single-cell RNA sequencing and cellular indexing of transcriptomes and epitopes by sequencing, we observed increased memory B cells and reduced germinal center B cells with decreased clonality in pwMS. Double-negative memory B cells were increased in pwMS that transcriptionally resembled B cells with a lytic EBV infection.

Moreover, EBV-targeting memory CD8 T cells were detected in a subset of pwMS. We also detected increased EBV DNA in dcLNs and elevated viral loads in patient saliva. These findings suggest that EBV-driven B cell dysregulation is a critical mechanism in MS pathogenesis.
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