Primary Sjögren's syndrome and the type I interferon system

Curr Pharm Biotechnol. 2012 Aug;13(10):2054-62. doi: 10.2174/138920112802273290.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Autoantibodies / immunology
  • Dendritic Cells / immunology
  • Humans
  • Interferon Type I* / blood
  • Interferon Type I* / genetics
  • Interferon Type I* / immunology
  • Salivary Glands, Minor / immunology
  • Salivary Glands, Minor / pathology
  • Sjogren's Syndrome / blood
  • Sjogren's Syndrome / genetics
  • Sjogren's Syndrome / immunology*
  • Sjogren's Syndrome / pathology


  • Autoantibodies
  • Interferon Type I