Molecular Mechanisms Of The Autoimmune Lymphoproliferati

该项目基于我们的发现，即控制淋巴细胞程序性死亡或凋亡的分子中的基因突变是导致自身免疫性淋巴细胞增殖综合征（ALPS）的原因。ALPS是一种影响儿童的疾病，导致正常淋巴细胞稳态的丧失，从而导致淋巴腺和器官肿胀。因为淋巴细胞是介导免疫反应的主要细胞，所以这种过量的淋巴细胞导致对患者自身组织的病理性自身免疫攻击。我们已经确定了一种称为Fas（也称为APO-1或CD 95）的死亡诱导细胞表面受体和其他调节细胞凋亡的分子的突变。这些研究有望为自身免疫性疾病的分子机制提供新的见解，并揭示淋巴细胞程序性细胞死亡途径中的关键步骤。我们目前正在研究一类称为ALPS III型的患者，这些患者不显示Fas受体，其配体（Fas配体）或caspase-10的突变。我们正在使用各种分子分析来确定导致ALPS III型疾病的基因突变。

This project is based on our discovery that genetic mutations in molecules that control the programmed death, or apoptosis, of lymphocytes is responsible for the Autoimmune Lymphoproliferative Syndrome (ALPS). ALPS is a disease affecting children that leads to loss of normal lymphocyte homeostasis leading to swollen lymph glands and organs. Because lymphocytes are the primary cell mediating immune reactions, this excess of lymphocytes leads to a pathological autoimmune attack on the patient's own tissues. We have identified mutations in a death-inducing cell surface receptor termed Fas (also known as APO-1 or CD95) and in other molecules that regulate apoptosis. These studies promise to provide new insights into the molecular mechanisms that underlie autoimmune disease as well as revealing crucial steps in the pathway of programmed cell death in lymphocytes. We are presently studying a class of these patients called ALPS Type III which do not display mutations in the Fas receptor, its ligand (Fas ligand), or caspase-10. We are using a variety of molecular analyses to determine the gene mutation that underlies disease in ALPS Type III.