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

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.

Increased incidence of rheumatoid arthritis in multiple sclerosis

“…However, recent meta-analysis reports refute the association between Epstein–Barr virus infection and RA. [ 48 ] Lastly, some important information about laboratory or clinical data was not readily available in the administrative database, namely, the subtypes of each disease. Thus, the relationship between the different subtypes of MS (relapsing-remitting, primary progressive, or secondary progressive) and their relationship between the subtypes of RA (seropositive and seronegative) remain unclear.…”

The microbiome–systemic diseases connection

“…The human microbiome includes the collective of genomes from viruses, bacteria, archeae and fungi, but the focus of this review was on the bacterial composition in the gut and oral cavity, referred to as the gut and oral microbiome. The role of viruses in systemic diseases is extensively reviewed by others (Triantafyllopoulou and Moutsopoulos, 2007;Hanlon et al, 2014;Ball et al, 2015) and will only briefly be discussed here.…”

Human MHC-II with Shared Epitope Motifs Are Optimal Epstein-Barr Virus Glycoprotein 42 Ligands—Relation to Rheumatoid Arthritis

“…Nevertheless, other studies claim that no association between EBV infection and onset of RA is evident [ 110 , 125 , 126 ]. For example, findings by Sherina and colleagues, analyzing anti-viral antibodies in relation of ACPAs, smoking HLA-DRB1 alleles and clinical parameters, do not support the hypothesis of EBV involvement in RA onset [ 126 ].…”