Systematic review and meta-analysis of the sero-epidemiological association between Epstein-Barr virus and rheumatoid arthritis

Ball, R. J., Avenell, A., Aucott, L., Hanlon, P. and Vickers, M. A. (2015) Systematic review and meta-analysis of the sero-epidemiological association between Epstein-Barr virus and rheumatoid arthritis. Arthritis Research and Therapy, 17, 274. (doi: 10.1186/s13075-015-0755-6) (PMID:26416719) (PMCID:PMC4587583)

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Abstract

Introduction: Infection with Epstein-Barr virus (EBV) has been suggested to contribute to the pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). We sought to determine whether prior infection with the virus occurs more frequently in patients with RA compared to controls. Methods: We performed a systematic review and meta-analyses of studies that reported the prevalence of anti-EBV antibodies in the sera of cases with RA and controls by searching Medline and Embase databases from 1946 to 2014, with no language restriction. Mantel-Haenszel odds ratios 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-three studies were included. Quality assessment found most studies reported acceptable selection criteria but poor descriptions of how cases and controls were recruited. When all studies were included, there was a statistically significant higher seroprevalence of anti-VCA IgG in patients with RA compared to controls with an odds ratio (OR) of 1.61 (95 % confidence interval (CI) 1.05–2.46, p = 0.03), which is a similar-sized summary OR to that reported for systemic lupus erythematosus (SLE). However, when studies were restricted to those reporting more plausible levels of exposure to EBV in the control groups, no significant association was apparent, OR 1.47 (95 % CI 0.88–2.46, p = 0.14). Using anti-EBNA 1 or anti-EA IgG as markers of previous infection also did not yield significant associations (OR 1.05, 95 % CI 0.68–1.61, p = 0.82; OR 2.2, 95 % CI 0.86–5.65, p = 0.10 respectively). Conclusions: Overall, these findings do not demonstrate an association between EBV seroprevalence and RA and therefore do not support the hypothesis that prior infection with EBV predisposes to the development of RA. This contrasts with meta-analyses that indicate EBV infection is associated with multiple sclerosis and SLE.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hanlon, Dr Peter
Authors: Ball, R. J., Avenell, A., Aucott, L., Hanlon, P., and Vickers, M. A.
College/School:College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > General Practice and Primary Care
Journal Name:Arthritis Research and Therapy
Publisher:BioMed Central
ISSN:1478-6354
ISSN (Online):1478-6362
First Published:First published in Arthritis Research and Therapy 17:274
Publisher Policy:Reproduced under a creative commons license

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