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      Current concepts on Sjögren's syndrome – classification criteria and biomarkers

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          Abstract

          Sjögren's syndrome is a lymphoproliferative disease with autoimmune features characterized by mononuclear cell infiltration of exocrine glands, notably the lacrimal and salivary glands. These lymphoid infiltrations lead to dryness of the eyes (keratoconjunctivitis sicca), dryness of the mouth (xerostomia), and, frequently, dryness of other surfaces connected to exocrine glands. Sjögren's syndrome is associated with the production of autoantibodies because B‐cell activation is a consistent immunoregulatory abnormality. The spectrum of the disease extends from an organ‐specific autoimmune disorder to a systemic process and is also associated with an increased risk of B‐cell lymphoma. Current treatments are mainly symptomatic. As a result of the diverse presentation of the syndrome, a major challenge remains to improve diagnosis and therapy. For this purpose an international set of classification criteria for primary Sjögren's syndrome has recently been developed and validated and seems well suited for enrolment in clinical trials. Salivary gland biopsies have been examined and histopathology standards have been developed, to be used in clinical trials and patient stratification. Finally, ultrasonography and saliva meet the need of non‐invasive imaging and sampling methods for discovery and validation of disease biomarkers in Sjögren's syndrome.

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          Cellular basis of ectopic germinal center formation and autoantibody production in the target organ of patients with Sjögren's syndrome.

          To investigate functional properties of the germinal center (GC)-like structures observed in salivary glands of patients with Sjögren's syndrome (SS) and to determine the frequency with which such structures develop. Hematoxylin and eosin-stained sections from 165 minor salivary gland biopsy samples were screened for GC-like structures. Expression of markers for GCs (CD3, CD20, Ki-67, CD35, CD31), adhesion molecules (intercellular adhesion molecule 1, lymphocyte function-associated antigen 1, vascular cell adhesion molecule 1, very late activation antigen 4), chemokines (CXCL13, CCL21, CXCL12), and production of autoantibodies (anti-Ro/SSA and anti-La/SSB) was investigated by immunohistochemistry. Apoptosis was investigated by TUNEL staining. GC-like structures were observed in 28 of 165 patients (17%). When GCs were defined as T and B cell aggregates with proliferating cells with a network of follicular dendritic cells and activated endothelial cells, such microenvironments were found in all patients in whom structures with GC-like morphology were observed. The defined microenvironments were not found in patients without apparent GC-like structures. The GCs formed within the target tissue showed functional features with production of autoantibodies (anti-Ro/SSA and anti-La/SSB) and apoptotic events (by TUNEL staining), and the local production of anti-Ro/SSA and anti-La/SSB autoantibodies was significantly increased (P = 0.04) in patients with GC development. Lymphoid neogenesis and functional ectopic GC formation take place in salivary glands of a subset of patients with SS. Our data suggest that the ectopic secondary lymphoid follicles contain all elements needed for driving the autoimmune response. Our findings underscore a key role for the target organ in recruitment of inflammatory cells and propagation of the disease process.
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            Prediction of Sjögren's Syndrome Years Before Diagnosis and Identification of Patients With Early Onset and Severe Disease Course by Autoantibody Profiling.

            Autoantibodies are highly characteristic of primary Sjögren's syndrome (SS) and represent important tools for studying its pathogenesis. Nonetheless, thus far, no systematic investigations have assessed the presence of autoantibodies before diagnosis. This study was undertaken to analyze how early and in what order autoantibodies appear, how predictive they are of primary SS, and whether they identify disease subsets.
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              Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology.

              E Tan (1988)
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                Author and article information

                Contributors
                roland.jonsson@uib.no
                Journal
                Eur J Oral Sci
                Eur. J. Oral Sci
                10.1111/(ISSN)1600-0722
                EOS
                European Journal of Oral Sciences
                John Wiley and Sons Inc. (Hoboken )
                0909-8836
                1600-0722
                03 September 2018
                October 2018
                : 126
                : Suppl Suppl 1 , Homage to 100 years of dental research in Scandinavia ( doiID: 10.1111/eos.2018.126.issue-S1 )
                : 37-48
                Affiliations
                [ 1 ] Broegelmann Research Laboratory Department of Clinical Science University of Bergen Bergen Norway
                [ 2 ] Department of Rheumatology Haukeland University Hospital Bergen Norway
                [ 3 ] Department of Clinical Dentistry – Section for Oral and Maxillofacial Radiology University of Bergen Bergen Norway
                [ 4 ] 2C SysBioMed Contra Switzerland
                [ 5 ] Gade Laboratory for Pathology Department of Clinical Medicine University of Bergen Bergen Norway
                [ 6 ] Department of Pathology Haukeland University Hospital Bergen Norway
                Author notes
                [*] [* ] Roland Jonsson, Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, N‐5021 Bergen, Norway

                E‐mail: roland.jonsson@ 123456uib.no

                Author information
                http://orcid.org/0000-0002-9588-0260
                http://orcid.org/0000-0003-0593-2731
                Article
                EOS12536
                10.1111/eos.12536
                6586012
                30178554
                3b678dba-24b7-4253-b246-fe927c54c30b
                © 2018 The Authors. Eur J Oral Sci published by John Wiley & Sons Ltd

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 03 May 2018
                Page count
                Figures: 5, Tables: 2, Pages: 12, Words: 10057
                Funding
                Funded by: Broegelmann Foundation
                Funded by: HarmonicSS
                Award ID: H2020‐SC1‐2016‐RTD/731944
                Funded by: Western Norway Regional Health Authorities
                Award ID: 912065
                Funded by: University of Bergen
                Categories
                Symposium Contribution
                Homage to 100 years of dental research in Scandinavia
                Symposium Contributions
                Custom metadata
                2.0
                eos12536
                October 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.4 mode:remove_FC converted:20.06.2019

                Dentistry
                biomarkers,classification,histopathology,sjögren's syndrome,ultrasonography
                Dentistry
                biomarkers, classification, histopathology, sjögren's syndrome, ultrasonography

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