Protein Markers to T1D Progression

描述(申请人提供)：1型糖尿病(T1D)是产生胰岛素的胰腺细胞自身免疫破坏的结果--一个长达数月至数年的无症状期。目前，针对胰岛细胞抗原的自身抗体用于识别那些T1D风险增加的人，但迫切需要更多的生物标记物来指示这种细胞破坏过程，并帮助理解疾病的发病机制。利用液质联用(LC-MS)的蛋白质组学技术，我们已经鉴定出一组与天然免疫反应相关的新的血清蛋白，并能以较高的灵敏度和特异性将T1D与健康对照区分开来。此外，这些标记中的大多数都是 不只是2型糖尿病引起的高血糖的结果。该项目的长期目标是为T1D提供完全有效的诊断和预后标记物，并获得对该疾病发病机制的更多见解。在目前的应用中，我们将把我们之前的生物标记物发现工作扩展到从T1D器官捐赠者获得的人胰腺组织，以及在T1D进展过程中收集的一系列血清样本，以全面鉴定与T1D疾病进展相关的新的蛋白质和蛋白亚型。这项新工作的发现，以及我们之前的数据，将使用从1型糖尿病预防(DPT-1)队列中纵向收集的血清样本来验证疾病早期诊断和预后。早期诊断和风险评估标准将建立在纵向变化的多肽标志物的基础上。

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.