The risk of systemic lupus erythematosus associated with Epstein-Barr virus infection: a systematic review and meta-analysis

Clin Exp Med. 2019 Feb;19(1):23-36. doi: 10.1007/s10238-018-0535-0. Epub 2018 Oct 25.

Abstract

Previous systematic reviews have found a higher sero-prevalence of EBV antibodies in SLE patients compared with controls. Because many studies have been published, there is a need to apply more precise systematic review methods. We examined the association between EBV and SLE patients by conducting a systematic review and meta-analysis of case-control studies that examined the prevalence of EBV antibodies and the DNA-positive rate. We searched the MEDLINE and EMBASE databases from 1966 to 2018 with no language restrictions. The Mantel-Haenszel odds ratios (OR) for EBV antibody sero-positivity were calculated, and meta-analyses were conducted. Quality assessment was performed using a modified version of the Newcastle-Ottawa scale, and 33 studies were included. Most studies found a higher sero-prevalence of VCA IgG and EA IgG in SLE patients compared with controls. Meta-analysis demonstrated a significantly higher OR for sero-positivity to VCA IgG and EA IgG for SLE cases (2.06 [95% confidence interval (CI) 1.30-3.26, p = 0.002] and 7.70, [95% CI 4.64-12.76, p < 0.001], respectively). The overall OR for the DNA-positive rate for SLE patients compared with controls was 3.86 (95% CI 1.52-9.83, p = 0.005). Other antibodies, i.e., VCA IgA/IgM, EBNA IgA, and EA IgA/IgM, also demonstrated a significant difference between SLE patients and controls. These findings support previous systematic reviews; however, publication bias cannot be excluded. The methodological conduct of studies could be improved, particularly when selecting controls and analyses of laboratory conduct.

Keywords: Epstein–Barr virus; Meta-analysis; Systemic lupus erythematosus.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antibodies, Viral / blood*
  • DNA, Viral / isolation & purification*
  • Epstein-Barr Virus Infections / complications*
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / immunology
  • Humans
  • Lupus Erythematosus, Systemic / epidemiology*
  • Prevalence
  • Risk Assessment

Substances

  • Antibodies, Viral
  • DNA, Viral