title: The complexity of Sjögren's syndrome: novel aspects on pathogenesis.
abstract: In Sjögren's syndrome, like in most other autoimmune diseases, the enigma leading to a pathogenic attack against self has not yet been solved. By definition, the disease must be mediated by specific immune reactions against endogenous tissues to qualify as an autoimmune disease. In Sjögren's syndrome the autoimmune response is directed against the exocrine glands, which, as histopathological hallmark of the disease, display persistent and progressive focal mononuclear cell infiltrates. Clinically, the disease in most patients is manifested by two severe symptoms: dryness of the mouth (xerostomia) and the eyes (keratoconjunctivitis sicca). A number of systemic features have also been described and the presence of autoantibodies against the ubiquitously expressed ribonucleoprotein particles Ro (Sjögren's-syndrome-related antigen A - SSA) and La (SSB) further underline the systemic nature of Sjögren's syndrome. The original explanatory concept for the pathogenesis of Sjögren's syndrome proposed a specific, self-perpetuating, immune mediated loss of acinar and ductal cells as the principal cause of salivary gland hypofunction. Although straightforward and plausible, the hypothesis, however, falls short of accommodating several Sjögren's syndrome-related phenomena and experimental findings. Consequently, researchers considered immune-mediated salivary gland dysfunction prior to glandular destruction and atrophy as potential molecular mechanisms underlying the symptoms of dryness in Sjögren's syndrome. Accordingly, apoptosis, fibrosis and atrophy of the salivary glands would represent consequences of salivary gland hypofunction. The emergence of advanced bio-analytical platforms further enabled the identification of potential biomarkers with the intent to improve Sjögren's syndrome diagnosis, promote the development of prognostic tools for Sjögren's syndrome and the long-term goal to identify possible processes for therapeutic treatment interventions. In addition, such approaches allowed us to glimpse at the apparent complexity of Sjögren's syndrome.
authors.affiliation: Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Bergen, Norway. roland.jonsson@gades.uib.no
authors.forename: Roland
authors.initials: R
authors.lastname: Jonsson
authors.forename: Petra
authors.initials: P
authors.lastname: Vogelsang
authors.forename: Roman
authors.initials: R
authors.lastname: Volchenkov
authors.forename: Alexander
authors.initials: A
authors.lastname: Espinosa
authors.forename: Marie
authors.initials: M
authors.lastname: Wahren-Herlenius
authors.forename: Silke
authors.initials: S
authors.lastname: Appel
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D015415:Biomarkers; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology; D007638:Keratoconjunctivitis Sicca / Q000150:complications / Q000276:immunology / Q000473:pathology; D051379:Mice; D053278:OX40 Ligand / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011976:Receptors, Muscarinic / Q000235:genetics / Q000276:immunology; D012261:Ribonucleoproteins / Q000276:immunology; D050797:STAT4 Transcription Factor / Q000235:genetics / Q000276:immunology; D012469:Salivary Glands / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D012859:Sjogren's Syndrome / Q000175:diagnosis / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology; D000099207:SS-A Antigen
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D050835:Interferon Regulatory Factors; D053278:OX40 Ligand; D010446:Peptide Fragments; D011976:Receptors, Muscarinic; D012261:Ribonucleoproteins; D050797:STAT4 Transcription Factor; D015534:Trans-Activators; D000099207:SS-A Antigen; C081976:EBF1 protein, human; C431713:IRF5 protein, human; C506261:SSB protein, human; C494090:STAT4 protein, human; C089251:TNFSF4 protein, human