Epstein-Barr Virus Causes Sjogren’s Syndrome

Smokers are more likely to have been infected by EBV, for socioeconomic reasons. The Surgeon General report of 2014 makes no mention at all of EBV in SS, therefore it is a deliberate act of scientific fraud.

Detection of Epstein-Barr virus-associated antigens and DNA in salivary gland biopsies from patients with Sjogren's syndrome. RI Fox, G Pearson, JH Vaughan. J Immunol 1986 Nov 15;137(10):3162-3168. "Cytoplasmic staining of epithelial cells (i.e., ductal and/or acinar cells) with monoclonal antibody against the EBV-encoded early antigen (EA-D) was noted in 8/14 salivary gland biopsies from SS patients. This antibody did not react with normal salivary glands or salivary gland tumors, nor with other tissues from SS patients." The reactive antigen was "similar to the EA-D antigen found in lymphoblastoid cells lytically infected with EBV." "Parotid saliva samples from 8/20 SS patients contained EBV DNA detectable by slot blot hybridization. EBV DNA was not detected in saliva of age-matched controls, rheumatoid arthritis patients lacking sicca symptoms, or patients with benign parotid tumors. The presence of EBV in salivary gland and saliva samples was associated with clinically more severe SS, as manifested by extraglandular symptoms such as vasculitis, occurrence of "pseudolymphoma", and marked abnormalities in immunoglobulin levels."

Fox - J Immunol 1986 abstract / PubMed

Detection of Epstein-Barr virus DNA by in situ hybridization and polymerase chain reaction in salivary gland biopsy specimens from patients with Sjögren's syndrome.X Mariette, J Gozlan, D Clerc, M Bisson, F Morinet. Am J Med 1991 Mar;90(3):286-294. "In situ hybridization detected EBV DNA in epithelial cells of labial salivary gland biopsy specimens from four of eight (50%) patients with primary SS, zero of six patients with secondary SS, and three of 39 (8%) control subjects. The difference between patients with primary SS and control subjects was statistically significant (p less than 0.02). The polymerase chain reaction detected EBV DNA in six of seven (86%) patients with primary SS, three of five (60%) patients with secondary SS, and seven of 24 (29%) control subjects. The difference between patients with primary SS and control subjects was statistically significant (p less than 0.01)."

Mariette - Am J Med 1991 abstract / PubMed

Analysis of antibody titers to Epstein-Barr virus nuclear antigens in sera of patients with Sjögren's syndrome and with rheumatoid arthritis.N Inoue, S Harada, N Miyasaka, A Oya, K Yanagi. J Infect Dis 1991 Jul;164(1):22-28. "By ELISA the average IgG antibody titers to domains of the five EBNAs, especially the amino-terminal domain of EBNA-2, in sera of patients with Sjögren's syndrome were slightly higher than those in normal sera. The tendency of sera from Sjögren's syndrome patients to have higher reactivities to the EBNA domains was also observed by immunoblotting."

Inoue - J Infect Dis 1991 abstract / PubMed

Epstein-Barr virus and the lacrimal gland pathology of Sjögren's syndrome. SC Pflugfelder, CA Crouse, D Monroy, M Yen, M Rowe, SS Atherton. Am J Pathol 1993 Jul;143(1):49-64. "EBV DNA was detected by in situ hybridization in intraductal epithelia in 13-33% of lobules in 21% of normal LGs and in cells in areas of B lymphoproliferation as well as the majority of epithelia in 86% of SS LGs. EBV genomic sequences were amplified from 36% of normal and 88% of SS LG biopsies by polymerase chain reaction. Only type 1 EBV sequences were amplified in SS LGs; in contrast EBV nuclear antigen 2-deleted but not type 1 sequences were amplified in normal LGs... No EBV antigens were detected in normal LGs. In contrast, latent antigens (latent membrane protein, EBV nuclear antigen 2) were detected in lymphocytes in areas of B lymphoproliferation, and early and late lytic cycle antigens were observed in epithelia in SS LGs. "

Pflugfelder - Am J Pathol 1993 full article landing page / PubMed Central

Sjögren's syndrome (SS) and Epstein-Barr virus (EBV) reactivation. I Toda, M Ono, H Fujishima, K Tsubota. Ocul Immunol Inflamm 1994;2(2):101-109. 157 simple dry eye with no circulating autoantibodies, 68 autoimmune positive dry eye, 62 dry eye associated with Sjögren's syndrome, and 47 healthy controls. "In SS, the mean antibody titers to EBV nuclear antigen (anti-EBNA), early antigen (anti-EA-IgG), and virus capsid antigen (anti-VCA-IgG) were significantly elevated compared to those of controls. No significant differences in antibody titers were found among ADE, SDE, and the controls. The EBV reactivated pattern was found in 17.7% of SS, which was significantly higher than the 4.4% in ADE, 1.9% in SDE, 0% in controls."

Toda - Ocul Immunol Inflamm 1994 abstract / PubMed

Association of Epstein-Barr virus (EBV) with Sjögren's syndrome: differential EBV expression between epithelial cells and lymphocytes in salivary glands. S Wen, N Shimizu, H Yoshiyama, Y Mizugaki, F Shinozaki, K Takada. Am J Pathol 1996 Nov;149(5):1511-1517. "The EBV-encoded small RNA-1 (EBER1) was detected in two of seven cases by in situ hybridization. The immunohistochemical staining of EBV proteins showed that the EBV latent membrane protein-1 was detected in four of seven cases and that BZLF1, BALF2, and gp350/220 proteins associating with virus production were not expressed. In eight controls, no positive signal was observed by these methods...EBER1-positive signals were exclusively localized on lymphocytes."

Wen - Am J Pathol 1996 full article landing page / PubMed Central

EBV reactivation serological profile in primary Sjögren's syndrome: an underlying trigger of active articular involvement? SG Pasoto, RR Natalino, HP Chakkour, S Viana Vdos, C Bueno, EP Leon, MB Vendramini, ML Neto, E Bonfa. Rheumatol Int 2013 May;33(5):1149-1157. 100 patients, 89 healthy controls. "Patients and controls had comparable frequencies and mean levels of anti-VCA IgG (90 vs. 86.5 %, p = 0.501; 2.6 ± 1.1 vs. 2.5 ± 1.1 AU/mL, p = 0.737) and anti-EBNA-1 IgG (92 vs. 94.4 %, p = 0.576; 141.3 ± 69.8 vs. 135.6 ± 67.5 RU/mL, p = 0.464). Anti-VCA IgM was negative in all cases. Noteworthy, higher frequency and increased mean levels of anti-EA-D were observed in patients than controls (36 vs. 4.5 %, p < 0.0001; 38.6 ± 57.4 vs. 7.9 ± 26.3 RU/mL, p < 0.0001)... joint activity was more frequent (25 vs. 9.4 %, p = 0.045) in anti-EA-D positive patients."

Pasoto - Rheumatol Int 2013 abstract / PubMed

Meta-analysis of differentially expressed genes in primary Sjogren's syndrome by using microarray. GG Song, JH Kim, YH Seo, SJ Choi, JD Ji, YH Lee. Hum Immunol 2014 Jan;75(1):98-104. 37 cases and 33 controls. "The up-regulated gene with the largest effect size (ES) (ES=-2.4228) was SELL (selectin L), whose product is required for the binding and subsequent rolling of leucocytes on endothelial cells to facilitate their migration into secondary lymphoid organs and inflammation sites. The most significant enrichment was in the immune response GO category (P=2.52×10(-25)). The most significant pathway in our KEGG analysis was Epstein-Barr virus infection (P=9.91×10(-06))."

Song - Hum Immunol 2014 abstract / PubMed

Infection and autoimmunity in Sjogren's syndrome: A clinical study and comprehensive review. S Kivity, MT Arango, M Ehrenfeld, O Tehori, Y Shoenfeld, JM Anaya, N Agmon-Levin. J Autoimmun 2014 Jun;51:17-22. 82 consecutive patients with SS, and 139 healthy controls. "An immune response (IgG) against Epstein-Barr virus (EBV) early antigen (EA) was positively associated with SS (OR 4; 95% CI: 1.82-8.83, p = 0.001) while a protective effect of IgG anti-cytomegalovirus (CMV) was observed (OR 0.3; 95%CI: 0.16-0.74, p = 0.009). Anti-Ro/SSA, anti-LA/SSB, anti-nuclear, anti-gliadin, anti-TTG-IgG and anti-RNP antibodies were statistically more prevalent among SS patients than controls. Notably, the presence of anti-Ro/SSA and anti La/SSB correlated with anti-EBVEA IgG (OR 3.1; 95%CI: 1.08-8.74) and (OR 3.9; 95%CI: 1.37-10.96) respectively."

Kivity - J Autoimmun 2014 abstract / PubMed

Implication of Epstein-Barr virus infection in disease-specific autoreactive B cell activation in ectopic lymphoid structures of Sjogren's syndrome. C Croia, E Astorri, W Murray-Brown, A Willis, KA Brokstad, N Sutcliffe, K Piper, R Jonsson, AR Tappuni, C Pitzalis, M Bombardieri. Arthritis Rheumatol 2014 Sep;66(9):2545-2557. EBV dysregulation within inflammatory infiltrates was observed exclusively in ectopic lymphoid structures of Sjogren's syndrome salivary glands "as revealed by EBV latent [EBER transcripts and EBER+ cells and immunoreactivity for EBV latency (LMP1, LMP2A)] and lytic (BFRF1) infection in B-cells and plasma cells, respectively... Importantly, perifollicular plasma cells displaying Ro52 immunoreactivity were frequently infected by EBV. Furthermore, ELS-containing SS-SG transplanted into SCID mice supported the production of anti-Ro52/La48 and anti-EBV antibodies but not ACPA. Analysis of CD4+ and CD8+ T-cell localization and granzyme-B (GrB) expression demonstrated that EBV persistence in ELS-containing SS-SG was associated with follicular exclusion of CD8+ T-cells and impaired CD8-mediated cytotoxicity."

Croia - Arthritis Rheumatol 2014 abstract / PubMed

Targeting the Ca2+ Sensor STIM1 by Exosomal Transfer of Ebv-miR-BART13-3p is Associated with Sjögren's Syndrome. GI Cruz, X Shao, H Quach, KA Ho, K Sterba, JA Noble, NA Patsopoulos, MP Busch, DJ Triulzi, WS Wong, BD Solomon. EBioMedicine 2016 Jun 29 [Epub ahead of print]. "We report herein that an EBV-specific microRNA (ebv-miR-BART13-3p) is significantly elevated in salivary glands (SGs) of pSS patients and we show that it targets stromal interacting molecule 1 (STIM1), a primary regulator of the store-operated Ca2+ entry (SOCE) pathway that is essential for SG function, leading to loss of SOCE and Ca2+-dependent activation of NFAT. Although EBV typically infects B cells and not salivary epithelial cells, ebv-miR-BART13-3p is present in both cell types in pSS SGs. Importantly, we further demonstrate that ebv-miR-BART13-3p can be transferred from B cells to salivary epithelial cells through exosomes and it recapitulates its functional effects on calcium signaling in a model system."

Cruz - EBioMedicine 2016 abstract / PubMed
Cruz / EBioMedicine 2016 full article

See Also:

Viruses Cause Salivary Gland Cancers
Epstein-Barr Virus Causes Nasopharyngeal Cancer
Epstein-Barr Virus Causes Lymphomas
EBV Causes Interstitial Lung Disease
Epstein-Barr Virus Causes Gastric Carcinoma
EBV Causes Lymphoepithelioma-like Lung Cancer
EBV Causes Mental Impairment in Children
EBV & Socioeconomic Status
EBV Causes Lupus
EBV Causes Multiple Sclerosis
EBV and Other Diseases


cast 07-30-16