title: Infection and autoimmunity in Sjogren's syndrome: a clinical study and comprehensive review.
abstract: Sjögren's syndrome (SS) is an autoimmune disease characterized primarily by lymphocytic infiltration of the exocrine glands, and autoantibody production. Multiple environmental factors affecting an individual with a genetic susceptibility may trigger the development of SS. Herein, we aimed to evaluate links between the different pebbles in the mosaic of SS. Demographic, clinical data and blood samples were gathered from 82 consecutive patients with SS, and 139 healthy controls. Samples were analyzed for infectious serology and auto-antibodies as well as for relevant genetic mutations (TAP genes) and cytokines levels. 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. Autoantibodies, cytokines and several genetic markers correlated with clinical manifestation of SS. Our data suggest that infectious agents may play both a causative and protective role in the pathogenesis of SS. Moreover certain autoantibodies, cytokines and specific TAP alleles correlate with clinical manifestations of SS, and may enable better prediction and/or directed therapy once confirmed in future studies.
authors.affiliation: The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel; Rheumatic Disease Unit, Sheba Medical Center, Tel-Hashomer, Israel; The Dr. Pinchas Borenstein Talpiot Medical Leadership Program 2013, Sheba Medical Center, Tel-Hashomer, Israel. Electronic address: kivitys@gmail.com.
authors.forename: Shaye
authors.initials: S
authors.lastname: Kivity
authors.affiliation: The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel; Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia; Doctoral Program in Biomedical Sciences, Universidad del Rosario, Bogotá, Colombia.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Arango
authors.affiliation: The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel; Rheumatic Disease Unit, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Ehrenfeld
authors.affiliation: The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Israel.
authors.forename: Omer
authors.initials: O
authors.lastname: Tehori
authors.affiliation: The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel; Incumbent of the Laura Schwarz-Kip Chair for Research of Autoimmune Diseases, Sackler Faculty of Medicine, Tel-Aviv University, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Israel. Electronic address: shoenfel@post.tau.ac.il.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Shoenfeld
authors.affiliation: Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia.
authors.forename: Juan-Manuel
authors.initials: JM
authors.lastname: Anaya
authors.affiliation: The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Israel.
authors.forename: Nancy
authors.initials: N
authors.lastname: Agmon-Levin
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000276:immunology; D000913:Antibodies, Protozoan / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007239:Infections / Q000150:complications* / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012859:Sjogren's Syndrome / Q000175:diagnosis / Q000209:etiology*
chemical_list: D000907:Antibodies, Bacterial; D000913:Antibodies, Protozoan; D000914:Antibodies, Viral; D001323:Autoantibodies; D007074:Immunoglobulin G
keywords: Auto-antibodies; Autoimmunity; Genetics; Infections; Sjögren's syndrome