The Relationship between Epstein-Barr Virus Nuclear Antigen-1 and the Risk of Autoimmune Rheumatic Diseases: Insights from a Mendelian Randomization Analysis

Abstract

BackgroundNumerous studies have investigated a possible correlation between Epstein-Barr virus (EBV) and autoimmune rheumatic diseases (ARDs). However, establishing a cause-and-effect relationship remains a challenging endeavor. This study employs Mendelian randomization to examine the impact of EBV nuclear antigen-1 antibody (EBNA-1) antibody levels on the susceptibility to nine distinct ARDs, including rheumatoid arthritis (RA), primary Sjogren's syndrome (PSS), systemic lupus erythematosus (SLE), undifferentiated reactive arthritis (UA), systemic sclerosis (SSc), adult-onset Still's disease (AOSD), psoriatic arthritis (PsA), dermatomyositis (DM), and ankylosing spondylitis (AS). MethodsThe researchers applied a two-sample Mendelian randomization approach, utilizing online data from separate cohorts of European descent. We drew upon data from GWAS related to EBNA-1 antibody levels and the nine autoimmune-related disorders. Our primary analyses predominantly relied on the Inverse Variance Weighted methodology, complemented by a range of sensitivity assessments. ResultsOur analysis revealed significant direct associations between EBNA-1 antibody levels and the risk of developing PSS (95% CI: 0.44 to 0.85, p = 0.003), PsA (95% CI: 0.36 to 0.99, p = 0.044), AS (95% CI: 0.07 to 0.88, p = 0.031), and UA (95% CI: 0.56 to 0.96, p = 0.025). These results remained consistent through comprehensive sensitivity analyses. However, no clear associations were found for the other specified conditions. ConclusionsOur findings provide compelling evidence that EBNA-1 antibody levels play a role in developing ARDs. These findings enhance our understanding of ARD pathogenesis and hold substantial promise for developing potential treatment strategies.