Antibody Reprtoire Characterization in Celiac Disease

乳糜泻中的抗体库特征

基本信息

批准号：
8796822
负责人：
Patrick S Daugherty
金额：
$ 30.8万
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 2016-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8796822
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 Sensitivity and Specificity Serum Specificity System Technology Testing Therapeutic Time Tissues Toxic Environmental Substances Training Transglutaminases Validation Wheat accurate diagnosis base cohort cost cross reactivity detector disease diagnosis improved new technology novel outcome forecast pathogen personalized medicine prototype repository response screening 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.

描述（由申请人提供）：所提议的努力旨在改变基于抗体生物标志物的医学诊断范式，从而能够使用单一的廉价测试来诊断数百种流行疾病和病症。尽管抗体目前可作为多种疾病的优秀生物标志物，但在一次测试中很少评估多个抗体特异性。此外，当前大多数测量抗体生物标志物的测试在单独使用时通常不能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，我们将生成并临床验证可扩展抗体库分析微阵列在乳糜泻诊断、预测和治疗监测中的效用。利用高分辨率抗体特异性数据，新型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，将能够建立人类抗体特异性库数据库，为更好地了解疾病病因和乳糜泻和其他疾病的个性化治疗提供广泛适用的工具。这项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。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Identification of disease-specific motifs in the antibody specificity repertoire via next-generation sequencing.

通过下一代测序鉴定抗体特异性库中的疾病特异性基序。

DOI：
发表时间：
2016-08-02
期刊：
影响因子：
4.6
作者：
Pantazes, Robert J;Reifert, Jack;Bozekowski, Joel;Ibsen, Kelly N;Murray, Joseph A;Daugherty, Patrick S
通讯作者：
Daugherty, Patrick S

Prediction of antibody structural epitopes via random peptide library screening and next generation sequencing.

通过随机肽库筛选和下一代测序预测抗体结构表位。