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: 7478078
• 负责人: SHAHID HUSAIN
• 金额: $ 5.73万
• 依托单位: UNIVERSITY OF TORONTO
• 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 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7478078
• 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（由申请人提供）：Simkania negevensis 是一种类似衣原体的细胞内微生物，与婴儿和成人的呼吸道感染有关。在世界许多地方，接触这种生物体的现象很普遍。它可以在自来水中找到，并且可以在自由生活的变形虫中生长。局部宿主防御受损和免疫抑制强度较高使得肺移植（LTx）患者特别容易受到感染。我们在肺移植 (LTx) 患者的 40/41 支气管肺泡灌洗 (BAL) 样本中检测到了奈格沙门氏菌 DNA，但在免疫功能正常对照的 BAL 中未检测到。我们进一步研究了 19 例肺移植，其中 51 例连续 BAL，使用回归分析发现 S. negevensis 感染与发生急性排斥反应的可能性较高相关，但并未达到统计学显着性。这项试点研究的总体目标是获得数据，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。第二个目标是开发体外肺上皮细胞模型系统，在该系统中可以研究沙门氏菌感染对炎症细胞因子诱导和分泌的影响。为了实现主要目标，我们将检查来自各种临床状况（无排斥、急性排斥、慢性排斥）的 LTx 患者的 195 个 BAL 样本，寻找内格文西斯菌感染的证据，以确定肺部内格文西斯菌感染是否与这些情况相关。与此同时，肺炎衣原体将作为内部对照进行监测。第二个目标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。我们将使用 DNA 扩增和序列分析来比较在患者样本中检测到的 S. negevensis。检测到的生物体之间的巨大相似性将证明初步寻找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是否存在内盖文沙门氏菌 DNA，并与患者中检测到的生物体进行比较。

项目成果

Elevated CXCL10 (IP-10) in bronchoalveolar lavage fluid is associated with acute cellular rejection after human lung transplantation.

• DOI: 10.1097/tp.0b013e3182a6ee0a
• 发表时间: 2014-01-15
• 期刊: Transplantation
• 影响因子: 6.2
• 作者: Husain S;Resende MR;Rajwans N;Zamel R;Pilewski JM;Crespo MM;Singer LG;McCurry KR;Kolls JK;Keshavjee S;Liles WC
• 通讯作者: Liles WC

Simkania negevensis and acute cellular rejection in lung transplant recipients.

Simkania negevensis 和肺移植受者的急性细胞排斥。

• DOI: 10.1111/ctr.12571
• 发表时间: 2015
• 期刊: Clinical transplantation
• 影响因子: 2.1
• 作者: Jamal,AlainnaJ;Resende,MariangelaR;Prochnow,Taisa;McGilvray,Ian;Pilewski,JosephM;Crespo,MariaM;Singer,LianneG;McCurry,KennethR;Kolls,JayK;Keshavjee,Shaf;Liles,WConrad;Husain,Shahid
• 通讯作者: Husain,Shahid