Serological Evidence for the Association Between Epstein-Barr Virus Infection and Sjögren’s Syndrome

Abstract

Background: Exposure to Epstein-Barr virus (EBV) infection has been hypothesized to be an important risk factor for multiple rheumatic diseases, but the serological evidence so far for its role in Sjögren's syndrome (SjS) is not clearly established yet. This study aimed to assess the seroepidemiological associations of antibodies to EBV with SjS.Methods: A seroepidemiological study containing 119 patients with SjS and 65 healthy controls was first performed, in which the associations of SjS with four commonly studied EBV antibodies including IgM-anti-viral capsid antigen (anti-VCA) antibody, IgG-anti-VCA antibody, IgG-anti-early antigen (anti-EA) antibody, and IgG-anti-EBV nuclear antigen 1 (anti-EBNA1) antibody were evaluated. A systematic review and meta-analysis of eligible seroepidemiological studies was also carried out, and data syntheses were performed using random-effect meta-analysis.Results: In the case-control study, the patients with SjS had both a significantly higher prevalence of IgG-anti-EA antibody positivity (31.9% vs. 3.1%, P < 0.001) and high titers of IgG-anti-EA antibody (P < 0.001) than healthy controls. The titer of IgG-anti-VCA antibody was significantly increased in the patients with SjS compared with healthy controls (P < 0.001). IgG-anti-EA antibody seropositive patients with SjS had lower levels of both C3 (P = 0.002) and C4 (P = 0.02), and the titer of IgG-anti-EA antibody was inversely related to the levels of both C3 (r = -0.31, P < 0.001) and C4 (r = -0.20, P = 0.03). A total of 14 eligible studies on the serological associations between EBV infection and SjS were finally included into the meta-analysis, which suggested obvious associations of SjS with IgM-anti-VCA antibody [Odds ratio (OR) = 5.77, 95%CI 1.73-19.25, P = 0.004] and IgG-anti-EA antibody (OR = 9.97, 95%CI 4.58-21.67, P < 0.00001). Conclusions:The findings from this study provide strong serological evidence for the association between EBV infection and SjS. SjS has obvious associations with IgM-anti-VCA antibody and IgG-anti-EA antibody. IgG-anti-EA antibody is linked to low levels of C3 and C4 in the patients with SjS, the significance of which needs to be addressed in further studies.

Bioinformatics Analysis for Identification of Key Genes in Salivary Gland and the Potential of a Combination of Biomarkers for the Diagnosis of SS

“… 18 A previous study found that SS patients had a significantly higher prevalence of IgG-anti-EA and IgG-anti-VCA antibodies (which are specific in population with acute EBV infections) than healthy controls, and patients with SS that had higher levels of IgG-anti-EA antibodies, which were linked to low levels of C3 and C4, in a case-control study. 19 Interferon (IFN) plays an important role in both the pathophysiology and clinical manifestations of SS. 20 Most SS patients express a “type I IFN signature” in immune cells, which drive the production of auto-antibodies and a range of clinical manifestations.…”

From bedside to bench: how existing therapies inform the relationship between Epstein–Barr virus and multiple sclerosis

“…The autoreactive B cell hypothesis has also been proposed to drive systemic autoimmune diseases 21 . Elevated titres of one or more EBV antibodies have been identified in systemic lupus erythematosus, Sjogren's syndrome and rheumatoid arthritis 30–32 . As with MS, it is unclear whether differences in these antibody results implicate a role of EBV in autoimmune disease, or alternatively reflect differences in antibody production in patients with dysregulated immune systems.…”

“… 21 Elevated titres of one or more EBV antibodies have been identified in systemic lupus erythematosus, Sjogren's syndrome and rheumatoid arthritis. 30 , 31 , 32 As with MS, it is unclear whether differences in these antibody results implicate a role of EBV in autoimmune disease, or alternatively reflect differences in antibody production in patients with dysregulated immune systems. Even though single‐nucleotide polymorphisms shared across MS and other autoimmune disorders can be identified in genome‐wide association studies (GWAS), clinical overlap is not a common phenomenon (although case reports do exist).…”

Abnormal Changes of Monocyte Subsets in Patients With Sjögren’s Syndrome

“…SjS is a complex rheumatic disease characterized by the infiltration of immune cells into exocrine glands such as salivary glands, and effective targeted therapies for SjS are still lacking (1,2). Current studies suggest that some factors such as disease susceptibility genes, immune abnormalities, and viral infections are synergistically involved in its pathogenesis of SjS (3)(4)(5). Among those factors, abnormal immune factors such as B cell hyperactivity have been considered as key players in SjS pathogenesis and potential targets for SjS treatment (6,7).…”