The Roles of Tgf-B Signal and Inflammatory Cells in Mfs Patients and the Possible Correlation between Marfan Syndrome and Autoimmune Disease

Background: Marfan syndrome (MFS), a multisystem connective tissue disorder, results from mutations in FBN1 gene. This activates transforming growth factor β (TGF-β) signaling, which contributes to extracellular matrix (ECM) degeneration and leads to progressive aortic root dilatation. From clinical database, we find that several autoimmune diseases, such as ankylosing spondylitis, rheumatoid arthritis, systemic lupus erythematosus…etc, happened in MFS simultaneously. For the rarity of such coexistence, coincidence and not causal relationship of the symptoms and signs are suggested. Recent studies have defined the cytokine transforming growth factor-β (TGF-β) plays a critical role in peripheral T cell homeostasis, tolerance to self antigens, and T cell differentiation during the immune response. TGF-β promotes the differentiation of naive helper T-cells into Treg or Th17 and at the same time suppresses their differentiation to Th1 and Th2. Treg cells have anti-inflammatory properties and can cause quiescence of autoimmune disease. Increased Th17 cells activity and reduced functional activity of Treg cells result in an increased susceptibility to autoimmune disease. At present, there are still limited studies concerning the roles of T cells in MFS. Recently, some studies prove that T cells infiltrate in aortic walls of MFS, which may contribute to aortic aneurysm. Hypothesis: (1) patients with MFS loss of fibrillin-1 and lead to over-release of TGF-β, which promotes the differentiation of naive helper T-cells into Treg or Th17 and at the same time suppresses their differentiation to Th1 and Th2. (2) Increased Th17 cells activity and reduced functional activity of Treg cells may result in an increased susceptibility to autoimmune disease. Methods: 1. From 2000 to 2011 in our hospital and National Health data base, we will find the prevalence rate of autoimmune disease in Marfan syndrome and general population to see if there is obvious difference between these two groups. 2. Marfan syndrome (MFS, n = 20) and control non-MFS patients (n = 20) who are received aortic surgery due to aortic ectasia or aortic valve disease will be enrolled. Aortic specimens will be obtained for (1) immunohistochemical stain to define T cells, TGF-β and cytokine distribution; (2) in situ TUNEL test to define the degree of smooth muscle cells apoptosis. 3. MFS (n=30) and age / sex matched non-MFS (n=30) patients will be invited. 10 -20 ml peripheral blood sample will be collected to test circulating TGF-β, cytokine levels and T cells purification. After the completion of this study, we may characterize the roles of TGF-β signal and inflammatory cells in MFS patients and the possible correlation between Marfan syndrome and autoimmune disease. It may provide a way to find another treatment strategy to suppress aortic root dilatation and prolong life span by modulate T cells differentiation.