Diagnostic classifiers for sarcoidosis using a novel T7 phage display technology

使用新型 T7 噬菌体展示技术的结节病诊断分类器

• 批准号: 9805512
• 负责人: Lobelia Samavati
• 金额: $ 11.55万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9805512
• 关键词: Affect; African American; Age; Antibodies; Antigens; Autoantibodies; Bacterial Antigens; Bacteriophage T7; Bacteriophages; Biological Markers; Biopsy; Blood Tests; Bronchoalveolar Lavage; Cells; Clinical; Clinical Data; Collection; Complex; Cutaneous; Data; Development; Diagnosis; Diagnostic; Differential Diagnosis; Disease; Embryo; Enrollment; Epitopes; Etiology; Eye; Female; Fibroblasts; Future; Granuloma; Granulomatous; Human; Hypergammaglobulinemia; Immune System Diseases; Immunity; Immunoassay; Immunoglobulin G; Immunotherapy; Inflammatory; Leukocytes; Libraries; Lung; Mediastinal lymph node group; Messenger RNA; Methods; Modeling; Neuraxis; Organ; Pathogenesis; Patients; Performance; Phage Display; Plasma; Play; Population; Population Control; Predictive Value; Pulmonary Sarcoidosis; Role; Sampling; Sarcoidosis; Sensitivity and Specificity; Serological; Skin; Technology; Testing; Tissues; Training; United States National Institutes of Health; Validation; Viral Antigens; aged; anergy; base; biobank; biomarker panel; cDNA Library; case control; cohort; diagnostic biomarker; diagnostic panel; disease diagnosis; immune function; insight; instrument; monocyte; novel; novel therapeutics; patient response; predict clinical outcome; treatment response

Abstract Sarcoidosis is an inflammatory disease of unknown etiology that occurs worldwide and is characterized by granuloma formation in different organs. No specific test has been developed to diagnose this disease. Confirmation of non-caseating granuloma in tissue biopsy of involved organs in the absence of other causes is the current state of the art for diagnosing sarcoidosis. We propose to test the hypothesis that overall immunity plays a prominent role in the pathogenesis of sarcoidosis, since abnormalities of the immune function and the presence of various antibodies/autoantibodies occurs in this disorder. Using a high throughput method, we have developed a complex epitope library derived from materials of sarcoidosis patients. The epitopes are derived from a T7 phage cDNA library of potential sarcoidosis antigens using mRNA isolated from bronchoalveolar (BAL) cells and white blood cells (WBCs) of patients with sarcoidosis. This cDNA library containing large numbers of epitopes has been immunoscreened with sera from patients with sarcoidosis containing high titer IgG antibodies and the cloned phages have been used to construct an antigen microarray to detect antibodies against sarcoid antigen(s) in the sera of test subjects. We have identified a panel of biomarkers/classifiers with high sensitivity and specificity that can discriminate between sera of patients with sarcoidosis and healthy controls. In our study we used 80-90% of African American female population of sarcoidosis patients and these patients were not strictly age-matched with healthy controls. To test this hypothesis, we propose to use banked plasma from diversified population of sarcoidosis patients and aged-matched healthy controls, enrolled in the NIH-sponsored A Case Controlled Etiology of Sarcoidosis Study (ACCESS). We would like to use these plasma samples and the clinical data from ACCESS biorepository to first test and validate the bioreactivity of plasma obtained independently from cases and controls (ACCESS) to obtain a panel of diagnostic biomarkers/classifiers, which can discriminate between sarcoidosis and healthy controls. Second, we will determine whether the discovered biomarkers/classifiers can predict the clinical outcome and Scadding stages of sarcoidosis. In future, this approach could be used to identify a panel of biomarkers useful for diagnosis of various organ involvements in sarcoidosis and differential diagnosis of various granulomatous diseases or response to treatment in sarcoidosis subjects.

抽象的 结节病是一种未知病因的炎症性疾病，在世界范围内发生，是 以不同器官形成为特征。尚未开发特定的测试 诊断这种疾病。确认涉及的组织活检中非造成的肉芽肿 在没有其他原因的情况下，器官是诊断结节病的现行状态。 我们建议检验以下假设，即总体免疫力在 结节病的发病机理，因为免疫功能异常和存在 这种疾病发生了各种抗体/自身抗体。使用高吞吐量方法，我们 已经开发了一个复杂的表位文库，该文库源自结节病患者的材料。这 表位是源自使用潜在结节抗原的T7噬菌体cDNA库 从支气管肺泡（BAL）细胞和白细胞（WBC）中分离出的mRNA 结节病。这个包含大量表位的cDNA库已免疫镜 结节病患者的血清含有高滴度IgG抗体，克隆 噬菌体已用于构建抗原微阵列以检测针对曲折的抗体 测试受试者血清中的抗原。我们已经确定了一组生物标志物/分类器 高灵敏度和特异性可以区分结节病患者血清 和健康对照。在我们的研究中，我们使用了80-90％的非裔美国女性人口 结节病患者和这些患者并未严格与健康对照相匹配。到 检验这一假设，我们建议使用来自多元化的血浆 结节病患者和年龄匹配的健康对照，参加了NIH赞助的病例 结节病研究（访问）的控制病因。我们想使用这些等离子体 样本和从Access BioreSotor的临床数据首先测试并验证 独立于病例和对照（访问）获得的等离子体的生物反应性以获得 诊断生物标志物/分类器的面板，可以区分结节病和 健康控制。第二，我们将确定发现的生物标志物/分类器是否可以 预测结节病的临床结局和刺伤阶段。将来，这种方法可能 用于识别一组生物标志物，可用于诊断各种器官参与 各种肉芽肿性疾病的结节病和鉴别诊断或对 结节病受试者的治疗。