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

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Abstract

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.
Original languageEnglish
Article numberR3
JournalArthritis Research & Therapy
Volume16
Issue number1
DOIs
Publication statusPublished - 6 Jan 2014

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Human Herpesvirus 4
Systemic Lupus Erythematosus
Meta-Analysis
Confidence Intervals
Publication Bias
Viral Antigens
Capsid
Odds Ratio
Epstein-Barr Virus Infections
Antibodies
Seroepidemiologic Studies
Virus Diseases
Immunoglobulin A
Patient Selection
Language
Cross-Sectional Studies
Immunoglobulin G
Databases
Antigens
Serum

Cite this

@article{ce4dc26a7f23499db4368105ac56cdf8,
title = "Systematic review and meta-analysis of the sero-epidemiological association between Epstein-Barr virus and systemic lupus erythematosus",
abstract = "IntroductionInfection 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.MethodsWe 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.ResultsTwenty-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.ConclusionsOverall, 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.",
author = "Peter Hanlon and Alison Avenell and Lorna Aucott and Vickers, {Mark A}",
note = "Acknowledgements The authors would like to thank Xueli Jia and Canan Spengler for translating Chinese and Turkish papers, respectively. Funding The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate.",
year = "2014",
month = "1",
day = "6",
doi = "10.1186/ar4429",
language = "English",
volume = "16",
journal = "Arthritis Research & Therapy",
issn = "1478-6354",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Systematic review and meta-analysis of the sero-epidemiological association between Epstein-Barr virus and systemic lupus erythematosus

AU - Hanlon, Peter

AU - Avenell, Alison

AU - Aucott, Lorna

AU - Vickers, Mark A

N1 - Acknowledgements The authors would like to thank Xueli Jia and Canan Spengler for translating Chinese and Turkish papers, respectively. Funding The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate.

PY - 2014/1/6

Y1 - 2014/1/6

N2 - IntroductionInfection 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.MethodsWe 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.ResultsTwenty-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.ConclusionsOverall, 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.

AB - IntroductionInfection 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.MethodsWe 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.ResultsTwenty-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.ConclusionsOverall, 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.

U2 - 10.1186/ar4429

DO - 10.1186/ar4429

M3 - Article

VL - 16

JO - Arthritis Research & Therapy

JF - Arthritis Research & Therapy

SN - 1478-6354

IS - 1

M1 - R3

ER -