The role of Epstein–Barr virus infection in primary Sjögren's syndrome

Abstract

Purpose of review The purpose of this article is to draw attention to the role of Epstein–Barr virus (EBV) virus in the pathogenesis of the primary Sjögren's syndrome. The article introduces the problem of consequences of EBV acute infection, and its reactivation, in association with the immune response modulation by the virus and with an increased risk of developing systemic autoimmune diseases and EBV-associated cancers. Recent findings The knowledge about the mechanisms by which the virus may stay for years in a latent phase, unrecognized by the host response immune cells is constantly expanding. There are several mechanisms and theories about EBV influence on the autoimmune process in Sjogren's syndrome (pSS), including the similarity (molecular mimicry) between viral EBNA-2 protein and Ro-60 antigen or EBER-1 and EBER-2 viral proteins and La antigen. Summary The influence of EBV infection on the development and course of pSS has been proven. It has also been established that both EBV and pSS result in the increased risk of tumor (especially lymphoma) development. In the light of these findings, new ways to manage EBV infections are being sought. Optimal methods for assessing EBV infection status are being devised. Research also aims at finding therapies, which target EBV through the inhibition of the autoimmune process and of viral activity. The present article is an attempt to discuss the most important phenomena and elements linking EBV infection to the primary Sjögren's syndrome.

Overlapping Sjogren’s syndrome reduces the probability of reaching target in rheumatoid arthritis patients: a propensity score matched real-world cohort from 2009 to 2019

“…The role of Epstein-Barr (EB) virus infection has been depicted in the pathogenesis of both RA and SS [33,34]. Recent studies revealed the interaction between EB nuclear antigen 2 (EBNA2) and genetic loci associated with RA, EBNA-1 and Ro-60 antigen in SS [34,35].…”

“…The role of Epstein-Barr (EB) virus infection has been depicted in the pathogenesis of both RA and SS [33,34]. Recent studies revealed the interaction between EB nuclear antigen 2 (EBNA2) and genetic loci associated with RA, EBNA-1 and Ro-60 antigen in SS [34,35]. Besides, a strict relationship between chronic periodontitis and RA and a verified association between chronic periodontitis exposure and SS risk have also been demonstrated [36,37].…”

Serum immunoglobulin G4 in Sjögren’s syndrome: a pilot study

“…Among the environmental triggering factors, viral infections, especially with Epstein-Barr virus (EBV), play an important role in pSS pathogenesis. This DNA virus from Herpesviridae family targeted exclusively B cells, with predilection to the salivary glands, which may cause symptoms of dryness [8]. EBV has the ability of existing in both, the lytic and the latent phase of the infection.…”

“…This feature, along with several other mechanisms (e.g., molecular mimicry, T-cell costimulatory gene CD70 overexpression, production of viral IL-10, or possibility for impaired EBV-specific T-cell response) enables it to modulate host response, as well as immunoglobulin and autoantibody production. This, in turn, leads to the development of autoimmunity, and may also lead to the development of malignancies, especially lymphoma [8,9]. Hypocomplementemia predominantly of C4 and C3 component of complement is often found in autoimmune diseases, especially in pSS.…”

From Anti-EBV Immune Responses to the EBV Diseasome via Cross-reactivity

“…In addition, EBV has been implicated in a wide variety of diseases, including systemic lupus erythematosus (SLE), Sjögren's syndrome, multiple sclerosis (MS), myasthenia gravis (MG), rheumatoid arthritis (RA), autoimmune thyroid disorders, inflammatory bowel disease, celiac diseases, diabetes, Parkinson's disease, myopericarditis, dilated cardiomyopathy, and even death. [9][10][11][12][13][14] At the same time, anti-EBV antibody level was found to be higher in BL patients than in control subjects. 3,[15][16][17] High level of anti-EBV immunoglobulin G antibodies were also found in subjects with NPC, [18][19][20][21] with IgG reactivity increasing significantly with tumor stage 21 ; Hodgkin and non-Hodgkin lymphomas [22][23][24] ; precancerous gastric lesions 25 ; MS [26][27][28][29] ; RA [30][31][32] ; MG 33,34 ; and SLE, 29,31,34 among others.…”