Systematic review and meta-analysis of the sero-epidemiological association between Epstein-Barr virus and systemic lupus erythematosus

Introduction: Infection with Epstein-Barr virus (EBV) has been suggested to contribute to the pathogenesis of systemic lupus erythematosus (SLE). We sought to determine whether prior infection with the virus occurs more frequently in patients with SLE compared to matched controls. Methods: We performed a systematic review and meta-analyses of studies that reported the prevalence of anti-EBV antibodies in the sera from cases of SLE and controls by searching Medline and Embase databases from 1966 to 2012, with no language restriction. Mantel-Haenszel odds ratios (OR) for the detection of anti-EBV antibodies were calculated, and meta-analyses conducted. Quality assessments were performed using a modified version of the Newcastle-Ottawa scale. Results: Twenty-five case-control studies were included. Quality assessment found most studies reported acceptable selection criteria but poor description of how cases and controls were recruited. There was a statistically significant higher seroprevalence of anti-viral capsid antigen (VCA) IgG (OR 2.08; 95% confidence interval (CI) 1.15 - 3.76, p = 0.007) but not anti-EBV-nuclear antigen1 (EBNA1) (OR 1.45; 95% CI 0.7 to 2.98, p = 0.32) in cases compared to controls. The meta-analyses for anti-early antigen (EA) /D IgG and anti-VCA IgA also showed significantly high ORs (4.5; 95% CI 3.00 to 11.06, p < 0.00001 and 5.05 (95% CI 1.95 - 13.13), p = 0.0009 respectively). However, funnel plot examination suggested publication bias. Conclusions: Overall, our findings support the hypothesis that infection with EBV predisposes to the development of SLE. However, publication bias cannot be excluded and the methodological conduct of studies could be improved, with regard to recruitment, matching and reporting of blinded laboratory analyses.