Immunodiagnosis of Active Tuberculosis in HIV-infected Patients

HIV感染者活动性结核病的免疫诊断

基本信息

批准号：
8242741
负责人：
Adithya Cattamanchi
金额：
$ 15.24万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-09 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8242741
关键词：
Address Africa South of the Sahara Algorithms Antigens Area Biological Assay Biological Markers Biometry Biostatistical Methods Blood Bronchoalveolar Lavage Fluid CD4 Positive T Lymphocytes California Cause of Death Cellular Immunity Clinical Clinical Investigator Clinical Research Clinical Trials Complement Country Data Development Plans Diagnosis Diagnostic Disease Enrollment Enzyme-Linked Immunosorbent Assay Epidemiology Evaluation Fellowship Flow Cytometry Foundations Funding Future Goals Gold HIV HIV Infections Hospitals Immune response Immunologic Markers Immunological Diagnosis Immunologics Immunology Income Infection Instruction Interferon Type II Interferons International Laboratories Lead Longitudinal Studies Lung Measures Mentored Patient-Oriented Research Career Development Award Mentors Methods Microscopy Mission Monitor Mycobacterium tuberculosis National Heart, Lung, and Blood Institute Oral Participant Patients Performance Peripheral Pharmaceutical Preparations Pneumonia Predictive Value Pulmonary Tuberculosis Recruitment Activity Relapse Relative (related person)Research Research Design Research Infrastructure Research Personnel Research Priority Respiratory Tract Infections Role Sampling San Francisco Sensitivity and Specificity Site Specificity Specimen Sputum Surrogate Markers T memory cell T-Lymphocyte Testing Training Translational Research Treatment Efficacy Treatment outcome Tuberculosis Uganda Universities Validation Work abstracting base career career development cohort cost effectiveness cytokine drug development enzyme linked immunospot assay experience follow-up improved interest lung basal segment mortality mycobacterial novel novel marker novel strategies outcome forecast patient oriented peripheral blood programs research clinical testing respiratory response skills tool transmission process treatment response tuberculosis drugs tuberculosis treatment

项目摘要

DESCRIPTION (provided by applicant): This is an application for a K23 award for Dr. Adithya Cattamanchi, a pulmonologist at the University of California, San Francisco. This K23 award will provide Dr. Cattamanchi with the support necessary to accomplish the following goals: (1) to develop an indepenent patient-centered translational research career focused on tuberculosis (TB); (2) to conduct clinical investigations of immunodiagnostic tests for TB in an international setting; (3) to implement advanced biostatistical methods in clinical studies; and (4) to develop theoretical and practical skills in applied T-cell immunology. To achieve these goals, Dr. Cattamanchi has assembled a mentoring team comprised of a primary mentor, Dr. Phillip Hopewell, a leading expert in translational TB research, and three co-mentors: Dr. Laurence Huang, who conducts clinical investigations of the pulmonary complications of HIV; Dr. Dennis Osmond, an expert in study design and current state-of-theart biostatistical analysis; and Dr. Huyen Cao, an expert in applied T-cell immunology. Dr. Cattamanchi's research will focus on a lung-based approach to immunodiagnosis of active TB. The proposed research will expand on recent data suggesting that (1) local rather than peripheral T-cell cytokine responses can better discriminate active TB from both LTBI and other respiratory infections and (2) T-cell cytokine responses may be useful in monitoring response to TB treatment. The proposed study will enroll a large cohort of HIV-infected pulmonary TB suspects to address the following specific aims: (1) To compare the performance of local and peripheral T-cell interferon-gamma release assay responses for the diagnosis of pulmonary TB in HIV-infected patients with negative sputum smear microscopy and (2) To define the M. TB-specific T-cell cytokine profile during the course of TB treatment in HIV-infected patients with active pulmonary TB. The participants will be drawn from a separate, NHLBI-funded study of the causes of pneumonia in HIV-infected patients in Kampala, Uganda. Peripheral blood, BAL fluid, and oral wash specimens will be used to measure T-cell cytokine responses and stored for future immunologic analyses. This proposal is consistent with the NHLBI's mission to study pulmonary immune responses in HIVassociated pulmonary infections. The study may lead to new and improved approaches to diagnosing and treating active TB in sub-Saharan Africa and other parts of the world. RELEVANCE (See instructions): The study may lead to new and improved approaches to diagnosing and treating active TB in sub-Saharan Africa and other parts of the world. The study may also help identify new markers to predict response to TB therapy. This may help accelerate evaluation of new drugs, making them available at the bedside where they are urgently needed. (End of Abstract)

描述（由申请人提供）：这是加州大学旧金山分校肺科医生 Adithya Cattamanchi 博士的 K23 奖项申请。该 K23 奖项将为 Cattamanchi 博士提供实现以下目标所需的支持：(1) 发展独立的、以患者为中心的、专注于结核病 (TB) 的转化研究事业； (2) 在国际环境下开展结核病免疫诊断试验的临床研究；（3）在临床研究中实施先进的生物统计学方法； (4) 培养应用 T 细胞免疫学的理论和实践技能。为了实现这些目标，Cattamanchi 博士组建了一个指导团队，其中包括一位主要导师 Phillip Hopewell 博士（转化结核病研究的领先专家）和三位联合导师：Laurence Huang 博士（负责肺结核临床研究）艾滋病毒并发症； Dennis Osmond 博士，研究设计和当前最先进的生物统计分析专家；以及应用T细胞免疫学专家Huyen Cao博士。 Cattamanchi 博士的研究重点是基于肺部的活动性结核病免疫诊断方法。拟议的研究将扩展最近的数据，这些数据表明（1）局部而非外周 T 细胞细胞因子反应可以更好地区分活动性结核病与 LTBI 和其他呼吸道感染；（2）T 细胞细胞因子反应可能有助于监测对结核病的反应。结核病治疗。拟议的研究将招募大量 HIV 感染肺结核嫌疑人，以实现以下具体目标：(1) 比较局部和外周 T 细胞干扰素-γ 释放测定反应在 HIV 感染者肺结核诊断中的表现- 痰涂片镜检结果呈阴性的感染患者；以及 (2) 确定患有活动性肺结核的 HIV 感染患者在结核病治疗过程中的分枝杆菌特异性 T 细胞细胞因子谱。参与者将来自 NHLBI 资助的一项针对乌干达坎帕拉 HIV 感染者肺炎病因的独立研究。外周血、BAL 液和口腔洗液样本将用于测量 T 细胞细胞因子反应并储存以供将来的免疫分析。该提议符合 NHLBI 研究 HIV 相关肺部感染肺部免疫反应的使命。这项研究可能会为撒哈拉以南非洲和世界其他地区带来新的和改进的诊断和治疗活动性结核病的方法。相关性（参见说明）：该研究可能会为撒哈拉以南非洲和世界其他地区的活动性结核病的诊断和治疗带来新的和改进的方法。该研究还可能有助于确定新的标记物来预测结核病治疗的反应。这可能有助于加速新药的评估，使它们可以在急需的地方使用。（摘要完）