Quantitative Serum Antibody Specificity Screening in Celiac Disease

乳糜泻血清抗体特异性定量筛查

• 批准号: 7531456
• 负责人: Patrick S Daugherty
• 金额: $ 21.65万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-15 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7531456
• 关键词: Affinity; Antibodies; Antibody Repertoire; Antibody Specificity; Antigens; Autoantigens; Autoimmune Diseases; Autoimmune Process; Bacteriophages; Barley; Binding; Biochemical; Biological Markers; Biopsy; Celiac Disease; Cells; Cereals; Clinical; Color; Control Groups; Data Set; Detection; Development; Diabetes Mellitus; Diagnosis; Diagnostic; Diagnostic Reagent; Diagnostic Specificity; Diagnostic tests; Diet; Digestive System Disorders; Disease; Disease Marker; Evaluation; Exhibits; Exposure to; Facility Construction Funding Category; Family; Fingerprint; Flow Cytometry; Future; Generations; Gliadin; Gluten; Gold; Government; Health Systems Agencies; Immunity; Immunoglobulin A; Immunoglobulin G; In Vitro; Individual; Inflammation; Intestines; Invasive; Iodine-131 Human Serum Albumin; Label; Lead; Libraries; Ligands; Malignant Neoplasms; Measurement; Measures; Medical; Methodology; Methods; Molecular; Outcome Study; Pathogenesis; Pathology; Patient Monitoring; Patients; Pattern; Peptide Library; Peptides; Personal Satisfaction; Persons; Phage Display; Population; Process; Proteins; Proteomics; Public Health; Purpose; Range; Rate; Reagent; Relative (related person); Rheumatoid Arthritis; Rotavirus; Rye cereal; Sampling; Screening procedure; Sensitivity and Specificity; Serum; Serum Proteins; Source; Specificity; Standards of Weights and Measures; Symptoms; System; Techniques; Testing; Tissues; Toxin; Training; Transglutaminases; Vaccination; Wheat; Work; base; cost; cost effective; food allergen; improved; insight; member; novel diagnostics; novel strategies; pathogen; response; sensor; success

DESCRIPTION (provided by applicant): The primary objective of this work is to develop a proteomic analysis method and demonstrate its utility for economical diagnosis of Celiac Disease, a common autoimmune digestive disorder associated with intolerance to gluten present in wheat, barley, and rye grains. In addition, this work is expected to lead to a better understanding of the cause of Celiac Disease. This work will result in the identification large panel of peptide ligands that can serve as an inexpensive but comprehensive diagnostic reagent panel for Celiac Disease. These peptides will be identified using a new molecular screening methodology. Briefly, this project will involve i) fluorescent- labeling of serum components from patients with confirmed Celiac Disease and healthy control groups, ii) specificity-based screening of bacterial display peptide libraries against pooled serum antibody and total serum protein depleted of HSA and IgG/IgA, iii) identification of library selected clones for diagnostic array construction, and iv) training of the array to maximize diagnostic specificity and sensitivity relative to the control group. The diagnostic array will then be validated with an undiagnosed patient group presenting the symptoms of CD. PUBLIC HEALTH RELEVANCE: Existing methodologies for interrogating the diverse antibody specificities present in the circulating repertoire have yielded new insights and diagnostics for autoimmune diseases and cancer. The proposed approach could expand these capabilities providing greater information about disease pathology, and allowing for the generation of improved biochemical reagents to create more effective yet inexpensive diagnostic tests. This work will establish a new gold standard methodology for analysis of serum antibody specificities, as well as provide reagents to diagnose a common autoimmune disorder (Celiac Disease), and better understand its cause.

描述（由申请人提供）：这项工作的主要目的是开发一种蛋白质组分析方法，并证明其对乳糜泻的经济诊断的实用性，乳糜泻是一种常见的自身免疫性消化疾病，与对小麦、大麦和黑麦谷物中的麸质不耐受有关。此外，这项工作预计将有助于更好地了解乳糜泻的病因。这项工作将鉴定出大量的肽配体，这些配体可以作为廉价但全面的乳糜泻诊断试剂组。这些肽将使用新的分子筛选方法进行鉴定。简而言之，该项目将涉及 i) 对确诊乳糜泻患者和健康对照组的血清成分进行荧光标记，ii) 针对合并血清抗体和去除 HSA 和 IgG/ 的总血清蛋白对细菌展示肽库进行基于特异性的筛选IgA，iii) 鉴定文库选择的用于诊断阵列构建的克隆，以及 iv) 训练阵列以最大化相对于对照组的诊断特异性和灵敏度。然后，诊断阵列将通过表现出 CD 症状的未确诊患者组进行验证。公共卫生相关性：用于询问循环库中存在的多种抗体特异性的现有方法已经为自身免疫性疾病和癌症产生了新的见解和诊断。所提出的方法可以扩展这些能力，提供更多有关疾病病理学的信息，并允许生成改进的生化试剂以创建更有效且廉价的诊断测试。这项工作将为分析血清抗体特异性建立新的金标准方法，并提供诊断常见自身免疫性疾病（乳糜泻）的试剂，并更好地了解其病因。