Protein Markers to T1D Progression

T1D 进展的蛋白质标志物

• 批准号: 8716320
• 负责人: Qibin Zhang
• 金额: $ 50万
• 依托单位: BATTELLE PACIFIC NORTHWEST LABORATORIES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-05 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8716320
• 关键词: Address; Affect; Age; Antigens; Autoantibodies; Autoimmune Process; Biological Assay; Biological Markers; Cell physiology; Cells; Clinical; Data; Development; Diabetes Mellitus; Diabetes prevention; Diagnosis; Diagnostic; Disease; Disease Progression; Early Diagnosis; Event; Extracellular Protein; Future; Genetic Markers; Goals; Human; Hyperglycemia; Immune response; Incidence; Individual; Insulin; Insulin-Dependent Diabetes Mellitus; Intravenous; Islet Cell; Knowledge; Literature; Liver; Marker Discovery; Measures; Monitor; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Organ Donor; Pancreas; Pathogenesis; Pathology; Patients; Peptides; Process; Prognostic Marker; Protein Isoforms; Proteins; Proteome; Proteomics; Publishing; Reaction; Research; Resolution; Risk; Risk Assessment; Sampling; Sensitivity and Specificity; Serum; Serum Proteins; Specificity; Symptoms; Time; Tissue Sample; Tissues; Validation; Variant; base; biobank; candidate marker; clinical Diagnosis; cohort; disorder risk; endocrine pancreas development; insight; insulin dependent diabetes mellitus onset; islet; liquid chromatography mass spectrometry; novel; outcome forecast; peripheral blood; prevent; sex

DESCRIPTION (provided by applicant): Type 1 diabetes (T1D) results from autoimmune destruction of insulin-producing pancreatic ?- cells - a long asymptomatic period spanning many months to years. Currently, autoantibodies to islet cell antigens serve to identify those at increased risk for T1D, yet additional biomarkers are desperately in need to indicate this ?-cell destruction process and to help understanding the disease pathogenesis. Using liquid chromatography-mass spectrometry (LC-MS) based proteomics, we have identified a panel of novel serum proteins that are involved in the innate immune response, and can distinguish T1D from healthy controls with high sensitivity and specificity. In addition, most of these markers are not merely a result of hyperglycemia induced by type 2 diabetes. The long-term goal of this project is to provide thoroughly validated diagnostic and prognostic markers for T1D, and to gain additional insights into the pathogenesis of this disease. In the present application, we will extend our previous biomarker discovery effort to human pancreatic tissues obtained from T1D organ donors, and serial serum samples collected during the progression of T1D for a comprehensive identification of novel proteins and protein isoforms correlated to the progression of this disease. Findings from this new effort, along with our previous data, will be validated for disease early diagnosis and prognosis using longitudinally collected serum samples from the Diabetes Prevention Type 1 (DPT-1) cohort. Early diagnosis and risk assessment criteria will be established on the basis of the longitudinally changed peptide markers.

描述（由申请人提供）：1型糖尿病（T1 D）是由产生胰岛素的胰腺？细胞-一个很长的无症状的时期，跨越数月至数年。目前，胰岛细胞抗原的自身抗体用于识别T1 D风险增加的患者，但迫切需要其他生物标志物来表明这一点。细胞破坏过程，并帮助了解疾病的发病机制。使用液相色谱-质谱（LC-MS）为基础的蛋白质组学，我们已经确定了一组新的血清蛋白，参与先天免疫反应，并可以区分T1 D与健康对照具有高灵敏度和特异性。此外，这些标记中的大多数是 而不仅仅是2型糖尿病引起的高血糖症的结果。该项目的长期目标是为T1 D提供彻底验证的诊断和预后标志物，并获得对该疾病发病机制的更多见解。在本申请中，我们将把我们先前的生物标志物发现工作扩展到从T1 D器官供体获得的人胰腺组织，以及在T1 D进展期间收集的系列血清样品，用于全面鉴定与该疾病进展相关的新蛋白质和蛋白质同种型。这项新研究的结果，沿着我们以前的数据，将通过从1型糖尿病预防（DPT-1）队列中纵向收集的血清样本进行疾病早期诊断和预后的验证。早期诊断和风险评估标准将建立在纵向变化的肽标志物的基础上。