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: 7536092
• 负责人: DAVID MARTIN MURDOCH
• 金额: $ 11.23万
• 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/7536092
• 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; 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; Inflammation Mediators; Inflammatory; Institution; International; Investigation; Lung; Lung Inflammation; Lymphoid; Measures; 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）：本申请概述了默多克博士的四年计划，该计划旨在从事独立国际研究，重点关注艾滋病毒/艾滋病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、哲学博士）和威​​特沃特斯兰德大学 (WITS) 肺病学家 Charles Feldman（医学博士、博士）在南非约翰内斯堡开展的国际合作。杜克大学 HIV 免疫学家 Kent Weinhold 博士将加入此次合作。这些导师将指导默多克博士研究艾滋病毒感染者免疫重建不同阶段对结核病的肺室免疫反应。这项研究将建立在 UNC/WITS 合作的免疫重建炎症综合征 (IRIS) 研究项目的基础上，该项目于 2005 年启动。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 个月内进行。我们约翰内斯堡 IRIS 研究的初步数据表明，开始 ART 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疗法，其他人注意到在抗逆转录病毒疗法的头几个月肺结核（PTB）的发病率很高。 ART 后 PTB 的免疫发病机制仍然很大程度上未知。我们假设 ART 启动会引起肺室炎症状态，并可能导致 IRIS-PTB 的发展。为了检验这一假设，默多克博士将识别在 ART 前、ART 后早期（<3 个月）和 ART 后晚期（>12 个月）发生 PTB 的 HIV 感染者，并比较他们对 TB 的外周和肺部免疫特征。他还将表征结核病分离株的耐药性和毒力模式，并对现有 IRIS 研究中存储的样本进行 T 细胞表型分析。这些研究将有助于识别 IRIS 的免疫标记，并表征 HIV 个体（无论是在 IRIS 还是非 IRIS 免疫状态下）对结核病的宿主病原体免疫反应。默多克博士将在南非进行这些研究，并利用杜克大学、北卡罗来纳大学和 WITS 的资源。这些研究的结果将有助于我们对艾滋病毒/结核病合并感染的理解，对各种免疫抑制状态下的结核病管理具有重要意义。