Taking into consideration that different autoimmune diseases may share some common pathogenetic pathways, we hypothesized that STAT4, a susceptibility gene found to be associated with increased risk for systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, Sjögren's syndrome, Wegener's granulomatosis, Crohn's disease, and ulcerative colitis may also have a role in psoriasis.
STAT4, a transcription factor transmitting signals induced by several key cytokines, has recently been identified as a genetic risk factor for rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren's disease (SD), thus indicating that multiple autoimmune diseases may share common biochemical pathways that lead to immune deregulation.
Other genes shown to be implicated in SS lymphoproliferation include genes involved a. in inflammatory responses such as the NFκB regulator Tumor necrosis factor alpha-induced protein 3 (TNFAIP3) and the Leukocyte immunoglobulin-like receptor A3 (LILRA3) immunoreceptor, b.
Although no association has been found with the NF-kB gene itself, associations in TNFAIP3 and TNIP1 (both genome-wide significant), VCAM1 and IRAK1BP (both suggestive), point to genetic explanations for dysregulation of the NF-kB pathway in SS.
Our findings clearly demonstrate changes in levels of the protein and gene expression between healthy controls and SS patients, depicting a very weak positivity for TNFAIP3 in SS samples.
Although no association has been found with the NF-kB gene itself, associations in TNFAIP3 and TNIP1 (both genome-wide significant), VCAM1 and IRAK1BP (both suggestive), point to genetic explanations for dysregulation of the NF-kB pathway in SS.