Investigation of the roles of A disintegrin-like metalloproteinase with thrombospondin TYPE-1 motif in the pathogenesis of behcet disease

Behçet Disease (BD) is a multisystemic inflammatory vasculitis characterized by a wide clinical spectrum including recurrent oral and genital ulcers, ocular, mucocutaneous, articular, neurologic, vascular and gastrointestinal involvement. Significant organs involvements cause severe morbidity and mortality in patients in spite of treatment. Genetic, environment and immünological factors play roles in the pathogenesis of BD. Although intensive studies have been done on the immünological factors, the pathogenesis of BD is still completely unknown. At present there is no definitive cure for BD and there are no specific markers that can accurately predict disease progression and therapeutic response. This indicates the importance of more understanding of cellular and molecular mechanisms regulating the disease. A better understanding of cellular and molecular mechanisms playing roles in the pathogenesis of BD will allow the development of new therapeutic strategies to fight with the disease. ADAMTS (A disintegrin-like and metalloproteinase domain with thrombospondin-1 repeats) is a large family of proteoglycanase enzymes that show proteolytic activity towards hyalectan proteoglycans, such as aggrecan, brevican, neurocan, and versican. It has been known that the expression levels of ADAMTS proteases which cause articular cartilage loss and damage of endothelial tissue by degrading extracellular matrix (ECM) in arthritis, such as osteoarthritis (OA) and rheumatoid arthritis (RA), thrombosis, vascular aneurysm and atherosclerosis are upregulated by pro-inflamatory cytokines, such as TNF-α, IL-1β ve IL-6 which are important mediators play important roles in the pathogenesis of BD as well as other inflammatory arthritis and vasculitis and the disease progression is associated with aberrant cytokine expression. Although intensive studies have been done on immünlogical factors in BD, whether ADAMTS proteases associated with inflammatory process play roles in the pathogenesis of BD remains unknown so far. Therefore, in this study the aim of the determination of whether the expression levels of ADAMTS genes can be used as a prognostic biomarker and therapeutic target in BD is quite important. Our aim is to investigate the roles of ADAMTS proteases (ADAMTS-1, -4, -5, -8, 9 ve -15) in the pathogenesis of Behçet Disease (BD), which is a chronic immune-inflammatory multisystem disease. For this purpose, periferal blood mononuclear cells (PBMCs) were isolated from total blood obtained from 30 BD patients in active period and 30 healthy controls. The mRNA expression of ADAMTS (ADAMTS-1, -4, -5, -8, -9 and -15) genes in PBMC was measured through real-time PCR (qPCR). Revealing the potential roles of ADAMTS in the pathogenesis of BD for the first time; It would enable the use of ADAMTS as a potential prognostic biomarker and contributing to guiding. Keywords, BD, ADAMTS, ECM, PBMC, biomarker