Genetics of Sjögren's syndrome

Abstract

The pathogenesis of Sjögren’s syndrome has not been elucidated. There has been evidence that genetics play an important role in the development of this disease from earlier studies. However, till now only a number of genes have been identified to be associated with SS, and these have only a weak or moderate effect. In this review we summarize the findings of the genetics studies and emphasize the need of large multicenter projects that will increase the sample sizes to provide more meaningful associations, as is the case in other common autoimmune diseases.

Predicting lymphoma development in patients with Sjögren’s syndrome

“…These two main clinical predictors are, in any case, strictly linked to additional clinical, pathologic and laboratory proposed predictors of lymphoma in pSS [6][7][8][9][10][11][12][13][14]. These include other CV-associated features (glomerulonephritis, peripheral neuropathy) [15], a heavier involvement of MALT by SG biopsy [2][3][4][5][6][7][8][9]43,44], and laboratory features as monoclonal gammopathy and rheumatoid factor and its peculiar idiotypes, which also determine the pathophysiology of cryoglobulinemia [15] (Table 1).…”

Danger signals in oral cavity-related diseases

“…Versican activates TLR2/6 heterodimers and is regulated by type I IFN in lung tissue . This finding may have particular relevance to SS pathogenesis, since a subset of SS patients display an IFN gene signature . Significantly, two separate GWAS studies revealed a suggestive association between variants in the TNFAIP3 gene locus with SS .…”

“…This finding may have particular relevance to SS pathogenesis, since a subset of SS patients display an IFN gene signature . Significantly, two separate GWAS studies revealed a suggestive association between variants in the TNFAIP3 gene locus with SS . While the functional consequence of this is unclear at present, TNFAIP3 encodes a negative regulator of TLR signaling and dysregulation of TLR‐mediated networks could contribute to DAMP‐driven inflammation in disease.…”

“…Signaling through PRRs induces downstream activation of signaling pathways to modulate generally pro‐inflammatory responses, though polymorphisms can alter the signaling responses from PRRs. Indeed, recent studies have begun to associate links between polymorphisms in PRRs and the development of periodontal disease and SS …”

Pulmonary and Bronchiolar Involvement in Sjogren's Syndrome

“…The pathogenesis of SS is complex, but involves activated and dysregulated B lymphocytes, T cell activation and proliferation, 2,9 and to a lesser extent participation of dendritic cells, monocytes/macrophages, and natural killer (NK) cells in the inflammatory process. 2 Genetic (human leukocyte antigen [HLA] and non-HLA), [10][11][12][13][14] nongenetic factors, 1,15,16 and environmental stimuli (including viruses) 1,17,18 may trigger inflammation and B cell dysregulation. 15 Interactions among glandular vascular endothelial cells, glandular epithelial cells, and dendritic cells drive the immune response.…”