Antibody Reprtoire Characterization in Celiac Disease

乳糜泻中的抗体库特征

• 批准号: 8414834
• 负责人: Patrick S Daugherty
• 金额: $ 29.23万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 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/8414834
• 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; base; cohort; cost; cross reactivity; detector; disease diagnosis; improved; new technology; novel; outcome forecast; pathogen; prototype; public health relevance; repository; response; screening; socioeconomics; success; therapeutic vaccine; tool; vaccine efficacy; vaccine safety

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）：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。