Patients with primary Sjogren’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.
Keywords: Immune complexes, interferon-alpha, IRF5, minor salivary glands, plasmacytoid dendritic cells, primary Sjogren’s
syndrome, SSA/SSB, STAT4, type I interferon, primary Sjogren’s syndrome (pSS), etiopathogenesis, interferon (IFN) system, clinical manifestations, target cells.
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