Abstract
There is a great deal of evidence pointing to interferons (IFNs) as being key cytokines in the pathogenesis of different systemic autoimmune diseases, including primary Sjögren’s syndrome (pSS). In this disease, a large number of studies have shown that an overexpression of type I IFN, the ‘so-called’ type I IFN signature, is present in peripheral blood mononuclear cells, and that this finding is associated with the development of systemic extra-glandular manifestations, and a substantial production of autoantibodies and inflammatory cytokines. In contrast, the absence or a milder expression of type I IFN signature and low level of inflammatory cytokines characterizes patients with a different clinical phenotype, where the disease is limited to glandular involvement and often marked by the presence of widespread pain and depression. The role of type II (IFNγ) in this subset of pSS patients, together with the potentially related activation of completely different immunological and metabolic pathways, are emerging issues. Expression of both types of IFNs has also been shown in target tissues, namely in minor salivary glands where a predominance of type II IFN signature appeared to have a certain association with the development of lymphoma. In view of the role played by IFN overexpression in the development and progression of pSS, inhibition or modulation of IFN signaling has been regarded as a potential target for the therapeutic approach. A number of therapeutic compounds with variable mechanisms of action have been tested or are under consideration for the treatment of patients with pSS.
Highlights
Primary Sjögren’s syndrome is a systemic autoimmune disease predominantly affecting post-menopausal women
A secondary end point of this study is to investigate the effects of tofacitinib on salivary gland pathological changes and systemic inflammation
The key role of IFN signaling in the pathogenesis of primary Sjögren’s syndrome (pSS) has been largely proven, the precise pathological mechanisms triggered by different IFNs are far from being completely elucidated, and certainly need further investigation
Summary
Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease predominantly affecting post-menopausal women. Antigen HLA-DR and HLA-DQ isotypes, which are closely associated with pSS In addition to these human leukocyte alleles, several non-MHC genes have shown a significant association with the disease. Some of these susceptibility genes, such as Interferon regulatory factor 5 (IRF5), signal transducer and activator of transcription 4 (STAT4), and Interleukin. It has been postulated that these upregulated genes may play important roles in the pathogenesis of pSS by activating some crucial biological processes of the disease [15] Both IFN pathway activation and polymorphism of IFN signaling-related genes are not specific for pSS but are shared by other systemic autoimmune disorders [16]
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