Detailed characterization of the immune response to Epstein-Barr virus in multiple sclerosis and following B cell depleting treatment

ABSTRACT: B-cell-depleting therapies are increasingly used for the treatment of multiple sclerosis (MS). Here, we characterize the impact of BCDT on humoral and cellular immune response to Epstein-Barr virus (EBV) in persons with MS (pwMS). We find that EBV viral load does not differ between pwMS and HC. By contrast, distinct differences are found in both humoral and cellular EBV-specific immunity in MS. EBV-specific antibody titres are increased in pwMS, whereas cellular immunity diverges toward lower CD8+ T cell reactivity against lytic antigens, including BZLF1. Notably, during periods of disease activity, both CD4+ and CD8+ T cell responses to lytic antigens tend to be higher. In addition, BZLF1-specific T cell clones recognizing the peptide RAKFKQLL were the most clonally expanded population in the intrathecal compartment of a pwMS with high CSF T cell counts. BCDT reduces EBV viral load and is associated with pronounced reduction in CD8+ T cell responses to all lytic EBV antigens. These findings delineate distinct alterations in EBV-specific immunity in MS and demonstrate that BCDT modulates both viral load and T cell responses. The data support a potential role for CD8+ T cell clones targeting lytic EBV proteins in MS pathogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE352228 | GEO | 2026/10/27

REPOSITORIES: GEO