Antibody Reprtoire Characterization in Celiac Disease

描述(由申请人提供)：拟议的工作旨在改变基于抗体生物标记物的医疗诊断范式，使之能够使用单一廉价的测试来诊断数百种流行疾病和疾病。虽然抗体目前是几种疾病的很好的生物标志物，但很少在一次测试中评估几种以上的抗体特异性。此外，目前大多数测量抗体生物标记物的检测单独使用时，通常不能提供足够的诊断敏感性和特异性。为了解决这些问题，将使用一种基于活试剂的新的集成发现和阵列构建过程，同时描述循环抗体谱系的广谱特异性。为了证明这种方法的内在力量和潜在的广泛适用性，我们将产生并临床验证可扩展抗体谱谱微阵列用于诊断、预测和治疗监测腹腔疾病的效用。利用高分辨率抗体特异性数据，新的自身和非自身抗原将被识别为可能参与疾病发生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，将有助于建立人类抗体特异库数据库，为更好地了解疾病病因和个性化治疗腹腔和其他疾病提供广泛适用的工具。这一努力的成功将减少诊断测试的成本以及未诊断和误诊疾病的经济负担。 与公共卫生相关：拟议项目的目标是开发一种通用的、可扩展的方法，以大规模并行的形式快速、经济地描述患者抗体谱系的特异性，以诊断疾病。这项新技术将首先被应用于开发一种改进的诊断、早期发现腹腔疾病以及能够对患者进行风险预测和治疗监测的方法。然后，该方法可以直接扩展，为目前缺乏诊断技术的各种疾病创造低成本的诊断工具。)

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. )