HLA-dependent association between EBNA1 antibody levels and disability progression in multiple sclerosis.

Authors

Anna Karin Hedström, Olivia Thomas, Pernilla Strid, Jan Hillert, Ingrid Kockum, Tim Waterboer, Tomas Olsson, Lars Alfredsson

Published in

Journal of neurology, neurosurgery, and psychiatry. Jul 31, 2026. Epub Jul 31, 2026.

Abstract

Epstein-Barr virus (EBV) is strongly implicated in the development of multiple sclerosis (MS) but whether EBV-related immune responses are also relevant for disease progression after diagnosis remains unclear. We investigated whether Epstein-Barr nuclear antigen 1 (EBNA1) antibody levels are associated with disability progression in MS and whether this association is modified by human leucocyte antigen (HLA)-A*02:01 and HLA-DRB1*15:01.
We analysed 5706 patients with MS from two population-based Swedish studies with longitudinal follow-up in the Swedish MS registry. EBNA1 IgG levels were analysed as a continuous variable, expressed per one SD increase. The primary outcome was confirmed disability worsening (CDW). Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Effect modification by HLA-A*02:01 and DRB1*15:01 was assessed using interaction terms and stratified analyses. Secondary and sensitivity analyses included dichotomisation of EBNA1 levels, alternative progression outcomes, delayed-entry models and treatment-related analyses.
Higher EBNA1 antibody levels were associated with a reduced risk of CDW among individuals carrying both A*02:01 and DRB1*15:01 (HR 0.87, 95% CI 0.81 to 0.93), whereas associations were weaker or absent in other HLA strata. Findings were similar in secondary and sensitivity analyses.
Our findings suggest that EBV-related antibody responses may have prognostic relevance for MS progression in specific genetic contexts, highlighting the importance of host-virus interactions beyond disease onset.

PMID:
42538096
Bibliographic data and abstract were imported from PubMed on 01 Aug 2026.

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