Type 1 diabetes mellitus is a worldwide chronic disease of childhood. Its cause is an absolute deficiency of insulin secretion usually relate to T-cell mediated autoimmune destruction of the insulin producing beta cell of the pancreas. A high incidence of Type 1 diabetes has been reported in Puerto Rican children <15 years old: 18 cases/100,000 children per year. Recent studies have reported a defective expression of the apoptosis-inducing CD95 (Fas/APO-1) molecule in T and B-cells of type 1 patients, suggesting an impaired capacity of autoreactive lymphocytes to undergo CD95-mediated apoptosis-induing CD95 (Fas/APO-1) molecule in T and B cell of type 1 patients, suggesting an impaired capacity of autoreactive lymphocytes to undergo CD95-mediated apoptosis. Based on these observations we plan to evaluate the role of T-cell Fas-induced apoptosis in the pathogenesis of type 1 diabetes. Our goals are to quantify the expression of Fas (CD95/APO-1) and membrane bound Fas ligand (FasL) molecules on peripheral blood lymphocytes obtained from Puerto Rican children newly diagnosed with type 1 diabetes and at high risk of developing the disease as well as in children without a family history of diabetes (controls), and to assess whether decreased susceptibility of lymphocytes to Fas-FasL induced apoptosis can be used as immunological marker of Type 1 diabetes pathogenesis in vivo. To achieve these goals the following specific aims have been identified: (1) to compare the immunological profile of Puerto Rican children recently diagnosed and at high risk of developing type 1 diabetes with the immunological profile of children without a family history of diabetes (controls) and quantify the expression of Fas (CD95) in lymphocytes by flow cytometric analysis and compare Fas and FasL expressions across lymphocyte subset populations in type 1 patients, high risk subjects and controls; and (3) to determine the concentrations of soluble Fas and soluble Fas ligand in the serum of children recently diagnosed and at high risk of developing type 1 diabetes as well as in children without a family history of diabetes. It is expected that these studies will enhance our understanding of the role of Fas-Fas L-mediated apoptosis in the pathogenesis of type 1 diabetes mellitus, especially in a Puerto Rican population.
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