Non-radioactive Multiplexed Assays for Prediction/Diagnosis of T1D and Comorbid A

描述（由申请人提供）：1型糖尿病（T1D）影响着美国大约三百分之一的年轻人，并且每年的发病率都在增加。它主要是一种自身免疫性疾病，通常与其他严重的自身免疫性疾病如艾迪生氏症、乳糜泻和甲状腺疾病有关。目前的诊断方案使用基于放射性的检测方法，分别测量多种自身免疫标记物。有必要开发更好的检测方法来诊断/预测谁将发展为T1D，并监测疾病进展和治疗反应，特别是在有了预防或延迟T1D的有效治疗方法之后。拟议的SBIR项目的完成，与博士合作进行。Yu和Eisenbarth （Barbara Davis儿童糖尿病中心）的研究成果，将导致开发敏感的多重检测面板，具有必要的敏感性和特异性，用于识别糖尿病前期或近期发病的T1D病例，并检测相关的自身免疫性疾病。这些面板将使用灵敏的Meso Scale Diagnostics， LLC. (MSD) MULTI-ARRAY(R)检测技术，并将使用小体积患者血液样本同时检测多种自身免疫反应。该阵列将采用基于MSD(R)技术的胰岛素前抗体和胰岛素自身抗体（IAA）检测，该检测由我们的合作者开发，在多实验室比较研究中已被证明优于目前使用的IAA放射免疫检测。在随后的II期和III期开发之后，该检测板将适用于患者样本的广泛使用，与目前基于单一放射性的方法相比，具有更高的准确性、可重复性和通量，成本显著降低，但存在固有的监管和放射性废物管理问题。MSD检测格式还有助于开发护理点检测，当预防糖尿病的治疗方法进入临床实践时，可以对大量人群（例如在儿科医生办公室）进行筛查。

DESCRIPTION (provided by applicant): Type 1 Diabetes (T1D) affects an estimated one in three hundred young people in the U.S., with increasing annual incidence. It is primarily an autoimmune disease and is often associated with other serious autoimmune conditions such as Addison's, celiac, and thyroid diseases. Current diagnostic protocols use radioactivity-based assays, measuring multiple autoimmune markers individually. There is a need for the development of better tests to diagnose/predict who will develop T1D, and for monitoring disease progression and therapeutic responsiveness, especially once effective treatments to prevent or delay T1D become available. The completion of the proposed SBIR project, carried out in collaboration with Drs. Yu and Eisenbarth (Barbara Davis Center for Childhood Diabetes), will result in development of sensitive multiplexed assay panels with required sensitivity and specificity for identification of pre-diabetic or recent onset T1D cases, and detection of associated autoimmune diseases. These panels will use sensitive Meso Scale Diagnostics, LLC. (MSD) MULTI-ARRAY(R) detection technology and will use small volumes of patient blood samples to simultaneously detect multiple autoimmune responses. The arrays will incorporate an MSD(R) technology-based assay for pro-insulin and insulin auto-antibodies (IAA) developed by our collaborators that has been shown to outperform currently used IAA radioimmunoassay in multi-laboratory comparative studies. Following subsequent Phase II and III development, the assay panels will be suitable for widespread use with patient samples, providing high accuracy, reproducibility and throughput at significantly lower costs than current singleplex radioactivity-based methods with their inherent regulatory and radioactive waste management issues. The MSD assay format also lends itself to development of point of care assays, making the screening of large populations possible (e.g. in pediatricians' offices) when therapies for the prevention of diabetes enter clinical practice. PUBLIC HEALTH RELEVANCE: The goal of this project is to develop blood tests that will identify patients (primarily children and young adults) who will develop, or have developed, type 1 diabetes and a number of associated autoimmune diseases. The diagnostic tests developed using MSD's highly sensitive multiplex technology will enable doctors to move away from current approaches that use much larger amounts of patient samples to measure biomarkers individually and involve use of radioactivity.