Antibody Reprtoire Characterization in Celiac Disease

乳糜泻中的抗体库特征

基本信息

批准号：
8025324
负责人：
Patrick S Daugherty
金额：
$ 31.35万
依托单位：
UNIVERSITY OF CALIFORNIA SANTA BARBARA
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-01-15 至 2015-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8025324
关键词：
Achievement Address Affect Algorithms Allergens Antibodies Antibody Repertoire Antibody Specificity Antigen Targeting Antigens Autoantigens Autoimmune Diseases Bacteria Barley Biochemical Biological Assay Biological Markers Biopsy CD3 Antigens Celiac Disease Clinical Data Data Set Databases Detection Development Diabetes Mellitus Diagnosis Diagnostic Diagnostic Sensitivity Diagnostic Specificity Diagnostic tests Diet Disease Disease Progression Early Diagnosis Economic Burden Epitopes Etiology Family Gluten Goals Health Healthcare Human Immune Immunity Immunoglobulin G Individual Laboratories Life Measurement Measures Medical Methodology Methods Molecular Monitor Onset of illness Organism Outcome Patient Monitoring Patients Pattern Peptide Fragments Peptide Library Peptides Population Printing Process Production Proteins Reagent Recombinants Reproducibility Resolution Rheumatoid Arthritis Risk Rye cereal Sampling Screening procedure Sensitivity and Specificity Serum Specificity System Technology Testing Therapeutic Time Tissues Toxic Environmental Substances Training Transglutaminases Validation Wheat base cohort cost cross reactivity detector disease diagnosis improved new technology novel outcome forecast pathogen prototype repository response socioeconomics success therapeutic vaccine tool vaccine efficacy vaccine safety

项目摘要

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. )

描述（由申请人提供）：拟议的努力旨在根据抗体生物标志物改变医学诊断的范例，从而使用单个廉价测试来诊断数百种患病疾病和状况。尽管目前抗体是多种疾病的出色生物标志物，但很少在单个测试中评估过一些抗体特异性。此外，单独使用时，大多数测量抗体生物标志物的当前测试通常不会提供足够的诊断敏感性和特异性。为了解决这些问题，使用基于生物试剂的新型集成发现和阵列构造过程，将同时介绍循环抗体库的广泛特异性。为了证明这种方法的内在能力和潜在的广泛适用性，我们将生成并在临床上验证可扩展的抗体库谱分析微阵列的效用，以诊断，预后和对乳糜泻的治疗监测。使用高分辨率抗体特异性数据，新型的自我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靶标。将抗体检测试剂发现过程应用于多个国家中心的大量疾病队列中，将使能够建立人类抗体特异性库库数据库，从而提供了一种广泛适用的工具，可以更好地了解疾病的病因和针对腹腔和其他疾病的个性化治疗。这项工作的成功将减少诊断测试的成本以及未诊断和诊断疾病的经济负担。公共卫生相关性：拟议项目的目的是开发一种一般且可扩展的方法，以迅速和经济地介绍患者抗体曲目的特殊性，以大规模平行的形式以诊断疾病。这项新技术将首先应用于改善诊断，对腹腔疾病的早期检测以及使患者的风险预后和治疗监测。然后可以直接扩展该方法，以创建低成本的诊断工具，以用于缺乏当前诊断技术的广泛疾病。）