Antibody Reprtoire Characterization in Celiac Disease

描述（由申请人提供）：拟议的努力旨在改变基于抗体生物标志物的医学诊断范式，使数百种流行疾病和病症的诊断能够使用单一的廉价测试。虽然抗体目前作为几种疾病的优秀生物标志物，很少有超过几个抗体特异性评估在一个单一的测试。此外，测量抗体生物标志物的大多数当前测试在单独使用时通常不提供足够的诊断灵敏度和特异性。为了解决这些问题，将使用基于活试剂的新型集成发现和阵列构建过程同时分析广谱循环抗体库的特异性。为了证明这种方法的内在力量和潜在的广泛适用性，我们将产生和临床验证可扩展抗体库分析微阵列用于乳糜泻的诊断、诊断和治疗监测的效用。使用高分辨率的抗体特异性数据，新的自身和非自身抗原将被鉴定为可能参与疾病发作或进展的血清抗体的靶标。将抗体检测试剂发现过程应用于来自多个国家中心的大量疾病队列，将能够建立人抗体特异性库数据库，提供广泛适用的工具，以更好地了解疾病病因并个性化治疗乳糜泻和其他疾病。这一努力的成功将减少诊断测试的费用以及未诊断和误诊疾病的经济负担。 公共卫生相关性：拟议项目的目标是开发一种通用和可扩展的方法，以快速和经济地分析患者抗体库的特异性，以大规模并行格式诊断疾病。这项新技术将首先应用于开发更好的诊断，早期发现乳糜泻，以及使患者的风险预测和治疗监测。然后，该方法可以直接扩展到为目前缺乏诊断技术的广泛疾病创建低成本诊断工具。)

DESCRIPTION (provided by applicant): The proposed effort aims to change the paradigm of medical diagnostics based upon antibody biomarkers, enabling diagnosis of hundreds of prevalent diseases and conditions using a single inexpensive test. Although antibodies presently serve as excellent biomarkers for several diseases, seldom are more than a few antibody specificities assessed in a single test. Furthermore, most current tests that measure antibody biomarkers typically do not provide sufficient diagnostic sensitivity and specificity when used alone. To address these problems, the specificities of a broad spectrum of the circulating antibody repertoire will be profiled simultaneously, using a novel integrated discovery and array construction process based upon living reagents. To demonstrate the intrinsic power and potential broad applicability of this approach, we will generate and clinically validate the utility of expandable antibody repertoire profiling microarrays for diagnosis, prognostication, and therapeutic monitoring of Celiac Disease. Using high-resolution antibody specificity data, novel self- and non-self antigens will be identified as the targets of serum antibodies that may be involved in disease onset or progression. Application of the antibody detection reagent discovery process to a large number of disease cohorts from multiple national centers will enable establishment of the human antibody specificity repertoire database, providing a broadly applicable tool to better understand disease etiology and personalize therapy for Celiac and other diseases. Success of this effort will reduce the cost of diagnostic tests and the economic burden of undiagnosed and misdiagnosed disease. PUBLIC HEALTH RELEVANCE: The objective of the proposed project is to develop a general and scalable methodology to rapidly and economically profile the specificities of the repertoire of patient antibodies in a massively parallel format to diagnose disease. This new technology will first be applied to develop a improve diagnosis, early detection of Celiac Disease as well as to enable risk prognostication and therapeutic monitoring of patients. The method could then be directly extended to create low-cost diagnostic tools for a broad range of diseases for which current diagnostic technology is lacking. )