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Primary Sjögren's syndrome and the type I interferon system.
MedLine Citation:
PMID:  22208657     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Patients with primary Sjögren's syndrome (pSS) have an activated type I interferon (IFN) system that contribute to the etiopathogenesis and clinical manifestations of the disease. The type I IFN system consists of the stimuli for type I IFN production, the receptors, cells and transcription factors involved in the synthesis of type I IFNs, the type I IFN-receptor and the effects on target cells. Increased type I IFN activity has been demonstrated in sera from patients with pSS and IFN-α, the main type I IFN, has been detected in the minor salivary glands. Gene expression profiling of peripheral blood mononuclear cells (PBMCs) and minor salivary glands from pSS patients display an up-regulation of type I IFN-induced genes, an "IFN signature". The professional IFN-α producing plasmacytoid dendritic cell (pDC) shows a reduced frequency in the peripheral blood, but has been detected in the salivary glands, possibly due to tissue recruitment. Polymorphisms in the interferon regulatory factor 5 (IRF5) and signal transducer and activator of transcription 4 (STAT4) genes in the type I IFN system, are associated with increased risk for pSS. A postulated disease model is that an initial viral infection induces type I IFN production in the salivary glands with subsequent activation of the adaptive immune system resulting in the production of autoantibodies against the RNA-binding proteins SSA/SSB/RNP. Interferogenic immune complexes are formed, which trigger the pDCs to an ongoing type I IFN production, which sustain the disease process. Potential therapeutic targets can be identified within the type I IFN system.
Authors:
Gunnel Nordmark; Maija-Leena Eloranta; Lars Rönnblom
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-2
Journal Detail:
Title:  Current pharmaceutical biotechnology     Volume:  -     ISSN:  1873-4316     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100960530     Medline TA:  Curr Pharm Biotechnol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Rheumatology clinic, Entrance 30, Uppsala University Hospital, SE-75185 Uppsala, Sweden. Gunnel.Nordmark@medsci.uu.se.
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