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

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

Zhao-Xia Li  1 , Shan Zeng  1 , Hui-Xia Wu  1 , Yi Zhou  2
Affiliations
Meta-Analysis

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

Zhao-Xia Li et al. Clin Exp Med. 2019 Feb.

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.

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Conflict of interest statement

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All analyses were based on previous published studies; thus, no ethical approval is required.

Informed consent

All analyses were based on previous published studies; thus, no informed consent is required.

Figures

Fig. 1
Fig. 1
Forest plot of ORs (a) and funnel plots with trim and fill (b) for anti-VCA IgG sero-positivity. The pseudo 95% confidence interval (CI) is computed as part of the analysis, which produces the funnel plot and corresponds to the expected 95% CI for a given standard error (SE)
Fig. 2
Fig. 2
Forest plot of ORs (a) and Begg’s Funnel Plot (b) for anti-EBNA IgG sero-positivity
Fig. 3
Fig. 3
Forest plot of ORs (a) and Begg’s funnel plot (b) for anti-EA IgG sero-positivity
Fig. 4
Fig. 4
Forest plot of ORs for DNA positivity and SLE
Fig. 5
Fig. 5
The linear dose–response relationship between the DNA-positive rate and SLE with average age as the explanatory variable. The solid line represents point estimates of the association between EBV DNA positivity and SLE; the dashed lines are 95% CIs. Circles present the dose-specific OR estimates reported in each study. The area in each circle is proportional to the inverse variance of the OR. The vertical axis is on a log scale
See this image and copyright information in PMC

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