Simkania Negevensis in Lung Transplant Inflammation and Rejection-A Pilot Study

Simkania Negevensis 在肺移植炎症和排斥反应中的初步研究

• 批准号: 7305716
• 负责人: SHAHID HUSAIN
• 金额: $ 7.86万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7305716
• 关键词: Acute; Adult; Allografting; Amoeba genus; Animal Model; Biological Models; Bronchiolitis; Bronchiolitis Obliterans; Bronchoalveolar Lavage; CCL2 gene; CXCL10 gene; Cell Line; Cell model; Cells; Chlamydia; Chlamydophila pneumoniae; Chronic; Clinical; Condition; Cultured Cells; DNA; DNA Sequence; DNA amplification; Data; Development; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Exposure to; Hospitals; Host Defense; Human; IL8 gene; Immunocompetent; Immunosuppression; Impairment; In Vitro; Infant; Infection; Infiltration; Inflammation; Inflammatory; Interferon Type II; Interleukin-1; Interleukin-10; Interleukin-13; Interleukin-4; Interleukin-6; Life; Link; Lung; Lung Transplantation; Macrophage Inflammatory Protein-1; Measures; Medical center; Messenger RNA; Modeling; Monitor; Needs Assessment; Nested PCR; Organism; Patients; Pilot Projects; Play; Polymerase Chain Reaction; Prevalence; Process; Prospective Studies; Purpose; RANTES; Regression Analysis; Research; Research Design; Respiratory Tract Infections; Role; Sampling; Sequence Analysis; Source; Specimen; Study models; Syndrome; T-Lymphocyte; Testing; Therapeutic immunosuppression; Transcriptional Activation; Transplant Recipients; Transplantation; Tumor Necrosis Factor-alpha; Universities; Up-Regulation; Water; base; chemokine; cytokine; drinking water; human TGFB1 protein; human TNF protein; in vivo; interleukin-12 subunit p40; internal control; macrophage; microorganism; neutrophil; novel; pathogen; response; water sampling

DESCRIPTION (provided by applicant): Simkania negevensis is a Chlamydia-like intracellular microorganism that has been associated with respiratory tract infection in infants and in adults. Exposure to the organism is prevalent in many parts of the world. It can be found in tap water and can grow in free-living amoebae. Impairment of local host defenses and a higher intensity of immunosuppression render lung transplant (LTx) patients uniquely susceptible to infections. We detected S. negevensis DNA in 40/41 bronchoalveolar lavage (BAL) samples from lung transplantation (LTx) patients, but not in BAL from immunocompetent controls. We further studied 19 lung transplants with 51 sequential BALs, using a regression analysis S. negevensis infection was associated with a higher likelihood of developing acute rejection which, however, did not reach statistical significance. The overall aim of this pilot study is to obtain data that will enable preliminary assessment of the need for an extensive prospective study of the involvement of this microorganism in LTx inflammation and rejection. A secondary aim is to develop an in vitro pulmonary epithelial cell model system in which the effect of S. negevensis infection on inflammatory cytokine induction and secretion can be studied. To achieve the main aim, we will examine 195 BAL samples from LTx patients in various clinical conditions (no rejection, acute rejection, chronic rejection) for evidence of S. negevensis infection in order to determine whether pulmonary S. negevensis infection is associated with these conditions. In parallel, Chlamydophila pneumoniae will be monitored as an internal control. The secondary aim will be achieved by study of the fate of the organism in bronchial epithelial cells in vitro, and its ability to induce inflammatory or profibrotic cytokine secretion. We will compare S. negevensis detected in patient specimens using DNA amplification and sequence analyses. Great similarity between organisms detected will justify a preliminary search for a possible common source of infection, i.e., testing tap water samples from the transplantation unit for S. negevensis DNA and comparison to that of organisms detected in patients.

描述（由申请方提供）：Simkania negevensis是一种衣原体样细胞内微生物，与婴儿和成人呼吸道感染相关。在世界许多地方，接触这种有机体的情况很普遍。它可以在自来水中找到，也可以在自由生活的阿米巴中生长。局部宿主防御功能受损和较高强度的免疫抑制使肺移植（LTx）患者特别容易感染。我们检测到S。在来自肺移植（LTx）患者的40/41支气管肺泡灌洗（BAL）样品中检测到negevensis DNA，但在来自免疫活性对照的BAL中没有。我们进一步研究了19例肺移植51个连续巴尔斯，使用回归分析S。Negevensis感染与发生急性排斥反应的可能性较高相关，但未达到统计学显著性。这项初步研究的总体目的是获得数据，以便初步评估是否需要对这种微生物参与LTx炎症和排斥反应进行广泛的前瞻性研究。第二个目的是建立一个体外肺上皮细胞模型系统，其中S。可以研究Negevensis感染对炎性细胞因子诱导和分泌的影响。为了达到主要目的，我们将检查195个来自不同临床状况（无排斥、急性排斥、慢性排斥）的LTx患者的BAL样本，以寻找S。negevensis感染，以确定是否肺S。内盖文感染与这些疾病有关。同时，将监测肺炎衣原体作为内部对照。次要目的将通过研究体外支气管上皮细胞中生物体的命运及其诱导炎症或促纤维化细胞因子分泌的能力来实现。我们将比较S。使用DNA扩增和序列分析检测患者标本中的Negevensis。检测到的微生物之间的高度相似性将证明初步搜索可能的共同感染源是合理的，即，检测移植单位的自来水样本中的沙门氏菌。negevensis DNA的DNA，并与患者中检测到的微生物进行比较。