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，从而从事独立国际研究职业，重点是艾滋病毒/艾滋病相关的肺结核和呼吸道感染。该提案的基础是南非约翰内斯堡的国际合作，在医学博士大卫·默多克（David Murdoch）之间，MPH，杜克大学（Duke University）的候选人，Annelies van Rie，医学博士，博士，一名北卡罗来纳大学（UNC）的传染病流行病学家（UNC）和Charles Feldman，MD，MD，MD，MD，MD，MD，PHD，PULMONSIOL，ATURMONS SUCIDAL，ATLEN，WITWAT）。杜克大学的艾滋病毒免疫学家肯特·韦恩霍尔德（Kent Weinhold）博士将加入这项合作。这些导师将监督默多克博士在研究HIV感染患者的免疫重建阶段对肺部室对结核病的免疫反应的研究。这项研究将建立在2005年启动的UNC/WITS协作免疫重建炎症综合征（IRIS）研究项目的基础上。IRIS通常在6个月内启动抗逆转录病毒疗法（ART）的HIV感染患者中观察到了一种自相矛盾的临床恶化。来自约翰内斯堡虹膜研究的初步数据表明，艾滋病毒患者发起的最常见的虹膜病原体是结核分枝杆菌（TB）。随着发展中国家最近引入的艺术，其他人注意到艺术的头几个月中肺结核（PTB）的发病率很高。 ART后PTB的免疫发病生成在很大程度上未知。我们假设艺术启动引起了肺部室的炎症状态，并可能有助于虹膜-PTB的发展。为了检验这一假设，默多克博士将识别出艾滋病毒感染的个体，这些人会在艺术品前（<3个月）前（<3个月）和图像后期（> 12个月），并比较其对TB的外围和肺免疫特征。他还将表征结核病分离株的耐药性和毒力模式，并对现有虹膜研究中的样品进行T细胞表型。这些研究将有助于鉴定虹膜的免疫标记，并表征艾滋病毒个体的宿主 - 病原体免疫反应，无论是在虹膜和非IRIS免疫状态下。默多克博士将在南非进行这些研究，并获得杜克大学，UNC和WITS的资源。这些研究的结果将有助于我们对HIV/TB共感染的理解，这对在各种免疫抑制状态的结核病管理具有重要意义。