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

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. Electronic supplementary material The online version of this article (10.1007/s10238-018-0535-0) contains supplementary material, which is available to authorized users.

Altered ratio of circulating follicular regulatory T cells and follicular helper T cells during primary EBV infection

“…Epstein-Barr virus (EBV) preferentially infects naïve B cells at oropharyngeal lymphoid tissues and subsequently establishes a persistent infection in the circulating memory B cells [1][2][3][4][5]. EBV is strongly associated with nasopharyngeal carcinoma, lymphoma and autoimmune diseases [6][7][8].…”

EBNA1 IgM-Based Discrimination Between Rheumatoid Arthritis Patients, Systemic Lupus Erythematosus Patients and Healthy Controls

“…In SLE patients, the following EBV antibodies have generally been found to be elevated: VCA IgM, IgA, IgG, EAD IgM, IgA, IgG, EBNA1 IgA [17,18,34,42,43,44,45,46,47,48,49]. A basic feature of EBV lifecycle is the ability of the virus to shift between (memory) B cell and epithelial cell infection.…”

“…Multiple genetic factors contribute to the development of SLE, but certain MHC II alleles are strongly predisposing albeit not the same as in RA [16]. Environmental factors overlap with those for RA to a large degree, and vitamin D, smoking and EBV infection have a major impact on disease development [11,17,18,19,20].…”

Novel Synthetic DNA Immunogens Targeting Latent Expressed Antigens of Epstein–Barr Virus Elicit Potent Cellular Responses and Inhibit Tumor Growth

“…It was first identified in a Burkitt lymphoma sample [6], and is now known to be a cause of Hodgkin’s lymphoma [7], nasopharyngeal carcinoma [8,9], and gastric carcinoma [10]. EBV infection is also linked to autoimmune disorders, such as multiple sclerosis [11] and systemic lupus erythematosus [12], which are likely tied to EBV-driven immune dysregulation [13]. The cancers associated with EBV are linked to their expression of EBV oncogenes, including Epstein–Barr virus nuclear antigen 1 (EBNA1) and latent membrane proteins 1 and 2 (LMP1 and LMP2) [14].…”