Journal of neurology, neurosurgery, and psychiatry
July 31, 2026 · via Europe PMC
HLA-dependent association between EBNA1 antibody levels and disability progression in multiple sclerosis.
Hedström AK, Thomas O, Strid P, Hillert J, Kockum I, Waterboer T, Olsson T, Alfredsson L
AI summary — for doctors, generated from the abstract only
Higher EBNA1 antibody levels were associated with slower disability progression in MS, but only in people carrying both HLA-A*02:01 and DRB1*15:01.
What was studied
Analysis of 5706 people with MS from two Swedish population-based studies linked to the national MS registry, relating EBNA1 IgG levels to confirmed disability worsening and testing modification by HLA genotype.
Key findings
- In double HLA carriers, each SD increase in EBNA1 IgG had a hazard ratio of 0.87 (95% CI 0.81 to 0.93) for confirmed disability worsening
- Associations were weaker or absent in other HLA groups
- Secondary and sensitivity analyses gave similar results
Clinical relevance
It suggests EBV immune responses may carry prognostic information after diagnosis in selected genetic backgrounds, relevant to neurologists counselling on progression.
Who should care
Limitations
Observational registry data cannot show causation, and the effect was modest and restricted to one genetic subgroup.
No change in practice; EBNA1 serology is not yet a validated prognostic test for individual patients.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
DOI
10.1136/jnnp-2026-338964
PMID
42538096
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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