The Role of Immune Reconstitution Inflammatory Syndrome (IRIS) in Pulmonary Tuber

免疫重建炎症综合征 (IRIS) 在肺结节中的作用

• 批准号: 7341785
• 负责人: DAVID MARTIN MURDOCH
• 金额: $ 11.21万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7341785
• 关键词: AIDS/HIV problem; Affect; African; Antigens; Basic Science; Blood Circulation; Bronchoalveolar Lavage; CD4 Lymphocyte Count; CD8-Positive T-Lymphocytes; Cell surface; Cells; Clinical; Clinical Investigator; Collaborations; Communicable Diseases; Count; DNA Sequence Rearrangement; Data; Deterioration; Developed Countries; Developing Countries; Development; Diagnosis; Doctor of Philosophy; Enrollment; Epidemiologist; Epidemiology; Exhibits; Extreme drug resistant tuberculosis; Foundations; Future; Generations; Goals; HIV; HLA-DR Antigens; Health; Immune; Immune response; Immunologic Markers; Immunologist; Immunology; Incidence; Individual; Infection; Inflammation; Inflammatory; Institution; International; Investigation; Localized; Lung; Lung Inflammation; Lymphoid; Measures; Mediator of activation protein; Memory; Mentors; Mononuclear; Multidrug-Resistant Tuberculosis; Mycobacterium tuberculosis; Newly Diagnosed; North Carolina; Organ; Patients; Pattern; Peripheral; Persons; Phenotype; Plasma; Play; Population; Predisposition; Production; Pulmonary Tuberculosis; Relative (related person); Research; Research Design; Research Personnel; Research Project Grants; Resistance; Resources; Respiratory Tract Infections; Risk; Role; Sampling; Screening procedure; South Africa; Specimen; Staging; Surface; Syndrome; T-Cell Activation; T-Cell Receptor; T-Lymphocyte; T-Lymphocyte Subsets; Testing; Training; Tuberculosis; Universities; Viral; Virulence; antiretroviral therapy; base; career; case control; pandemic disease; pathogen; peripheral blood; prevent; professor; reconstitution; response; restoration; skills; statistics

DESCRIPTION (provided by applicant): This application outlines a four year plan for Dr. Murdoch leading to a career in independent international research with a focus on HIV/AIDS-associated pulmonary TB and respiratory infections. The foundation for this proposal is an international collaboration in Johannesburg, South Africa between David Murdoch, MD, MPH, the candidate at Duke University, Annelies Van Rie, MD, PhD, an infectious disease epidemiologist at the University of North Carolina (UNC), and Charles Feldman, MD, PhD, a pulmonologist at the University of the Witwatersrand (WITS). Dr. Kent Weinhold, PhD, a HIV immunologist at Duke University, will join this collaboration. These mentors will supervise Dr. Murdoch in his study of the lung compartment immune response to TB during different stages of immune reconstitution in HIV-infected patients. This study will build upon the UNC/WITS collaborative immune reconstitution inflammatory syndrome (IRIS) research project initiated in 2005. IRIS is a paradoxical clinical deterioration observed in HIV-infected patients initiating antiretroviral therapy (ART), usually within 6 months. Preliminary data from our Johannesburg IRIS study indicates the most common IRIS pathogen in HIV patients initiating ART is Mycobacerium tuberculosis (TB). With the recent introduction of ART in developing countries, others have noted a high incidence of pulmonary tuberculosis (PTB) in the first months of ART. The immunopathogenesis of post-ART PTB remains largely unknown. We hypothesize ART initiation elicits an inflammatory state in the lung compartment and may contribute to the development of IRIS-PTB. To test this hypothesis, Dr. Murdoch will identify HIV-infected individuals who develop PTB pre-ART, early (<3 months) post-ART, and late (>12 months) post-ART, and compare their peripheral and lung immune profiles in response to TB. He will also characterize resistance and virulence patterns of the TB isolates and perform T cell phenotyping on stored samples from the existing IRIS study. These studies will help identify immune markers for IRIS and characterize the host-pathogen immune resonse to TB in HIV individuals, both in an IRIS and non-IRIS immune state. Dr. Murdoch will perform these studies in South Africa with access to the resources of Duke, UNC, and WITS. The results of these studies will contribute to our understanding of HIV/TB coinfection, with important implications on the management of TB in various immuosuppressive states.

描述（由申请人提供）：该申请概述了默多克博士的四年计划，该计划将导致他在独立的国际研究领域的职业生涯，重点是与HIV/ aids相关的肺结核和呼吸道感染。该提案的基础是杜克大学候选人David Murdoch，医学博士，公共卫生硕士，北卡罗来纳大学（UNC）传染病流行病学家Annelies Van Rie，医学博士，博士和Witwatersrand大学（WITS）的肺病学家Charles Feldman，医学博士，博士在南非约翰内斯堡的国际合作。杜克大学的HIV免疫学家Kent Weinhold博士将加入这项合作。这些导师将指导Murdoch博士研究hiv感染患者在免疫重建的不同阶段对结核病的肺间室免疫反应。这项研究将建立在2005年启动的UNC/WITS协同免疫重建炎症综合征（IRIS）研究项目的基础上。IRIS是在开始抗逆转录病毒治疗（ART）的hiv感染患者中观察到的一种矛盾的临床恶化，通常在6个月内。我们约翰内斯堡IRIS研究的初步数据表明，在开始抗逆转录病毒治疗的HIV患者中，最常见的IRIS病原体是结核分枝杆菌（TB）。随着最近在发展中国家引入抗逆转录病毒治疗，其他国家注意到在抗逆转录病毒治疗的头几个月肺结核发病率很高。抗逆转录病毒治疗后肺结核的免疫发病机制在很大程度上仍然未知。我们假设ART启动引发肺间室的炎症状态，并可能促进IRIS-PTB的发展。为了验证这一假设，Murdoch博士将确定在抗逆转录病毒治疗前、抗逆转录病毒治疗后早期（<3个月）和晚期（≤12个月）出现肺结核的hiv感染者，并比较他们对肺结核的外周和肺部免疫特征。他还将描述结核分离株的耐药性和毒力模式，并对现有IRIS研究中储存的样本进行T细胞表型分析。这些研究将有助于鉴定IRIS的免疫标记物，并表征HIV个体在IRIS和非IRIS免疫状态下对结核病的宿主-病原体免疫反应。默多克博士将利用杜克大学、北卡罗来纳大学和WITS的资源在南非进行这些研究。这些研究的结果将有助于我们对HIV/TB合并感染的理解，对各种免疫抑制状态下结核病的管理具有重要意义。