Abstract
IntroductionInfection 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.MethodsWe 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.ResultsTwenty-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).ConclusionsOverall, 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0755-6) contains supplementary material, which is available to authorized users.
Highlights
Infection with Epstein-Barr virus (EBV) has been suggested to contribute to the pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA)
In this study we present the first systematic review and meta-analysis of seropositivity for EBV among RA patients compared to controls
A higher degree of seropositivity was demonstrated in the RA group compared to the controls. This did not reach statistical significance with an odds ratio (OR) of 2.2 and the studies showed high heterogeneity with I2 = 79 % (p = 0.0001) (Fig. 4). This meta-analysis of case–control studies investigating the association between RA and serological markers of EBV infection failed to show a significant association between the disease and anti-viral capsid antigen (VCA) immunoglobulin G (IgG), anti-EBNA1 IgG or anti-early antigen (EA)
Summary
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. Claims that prior infection with Epstein-Barr virus (EBV) is important are of particular interest, as an association has been repeatedly demonstrated for multiple sclerosis (MS) [4] and a recent. Control of EBV infection has been suggested to be impaired in RA patients [6] with studies using real-time polymerase chain reaction (rt-PCR) techniques demonstrating EBV DNA loads in peripheral blood mononuclear cells greater than ten times those of normal controls [7]. Most notable is molecular mimicry, which was first suggested following the identification of serum from RA patients exhibiting reactivity against a nuclear antigen in EBV-infected lymphocytes, called the RA nuclear antigen (RANA) [8]. A second example of molecular mimicry was shown between the QKRAA amino acid motif of the β-chain of HLA-DR4 and EBV glycoprotein
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