Pathogen Specific Immunity in Sarcoidosis

结节病的病原体特异性免疫

• 批准号: 6926208
• 负责人: STEPHAN K SCHWANDER
• 金额: $ 19.31万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6926208
• 关键词: Mycobacterium tuberculosis; Propionibacterium; alveolar macrophages; biopsy; clinical research; cytotoxic T lymphocyte; diagnostic respiratory lavage; disease /disorder etiology; enzyme linked immunosorbent assay; gene expression; host organism interaction; human subject; immune response; immunologic memory; inflammation; interferon gamma; interleukin 10; lung disorder; microarray technology; microorganism antigen; monocyte; natural killer cells; patient oriented research; sarcoidosis

DESCRIPTION (provided by applicant): Since its initial description 125 years ago, sarcoidosis continues to be a "challenging" disease. Its etiology remains unknown. Discovering the etiology of sarcoidosis remains a major goal with important implications regarding treatment, predicting outcome, as well as determining approaches for preventive measures. Immunological responses and granulomatous tissue formation characterizing sarcoidosis are similar to those observed in a variety of infectious diseases. However, the nature of the specific antigen(s), which putatively trigger the inflammatory response in sarcoidosis, remains elusive. Occurrence of sarcoidosis in spatially related clusters, and household and health care settings strongly support person-to-person transmission of an infectious agent as one of the potential causes of this disease. Sarcoidosis has been associated with a variety of infectious agents, none of which can be cultured. Propionibacterium acne (P. acne) and M.tuberculosis (Mtb) are the most commonly identifiable infectious pathogens by PCR-based methods and considered to be associated with the development of this disease. Immunological studies in sarcoidosis have focused largely on the assessment of constitutive, immune responses and the description of the phenotypes of blood and lung cells in patients and control subjects. In this proposal we will utilize memory immune responses as search tools for the 'immunological imprints' from P. acne or Mtb exposure. Peripheral blood mononuclear cells and bronchoalveolar cells will be compared from patients with stage II and/or stage III sarcoidosis and from healthy control subjects. We will study by ELISPOT assay: (1) frequencies of pathogen-specific IFN-7-and IL-10-producing cells, and (2) utilizing P. acne- or Mtb-infected autologous monocytes and alveolar macrophages as target cells frequencies of pathogen-specific granzyme B-releasing cytotoxic T lymphocytes and natural killer cells. Finally, we will test the feasibility of identifying by DNA micro array, pathogen specific, transcriptional host gene expression profiles in P. acne- and Mtb-stimulated blood cells from healthy control subjects and patients with active sarcoidosis and to compare these with gene expression profiles from autologous, unstimulated in situ lung cells. Our studies will address the role of P. acne and Mtb in the etiology of sarcoidosis and will also serve as a basis or model for future work involving other possible infectious or non-infectious pathogens/antigens for the development of sarcoidosis.

描述（由申请人提供）：自125年前的最初描述以来，结节病仍然是一种“具有挑战性的”疾病。它的病因仍然未知。发现结节病的病因仍然是一个主要目标，其治疗，预测结果以及确定预防措施的方法的重要意义。免疫反应和表征结节病的肉芽肿组织形成与在多种传染病中观察到的相似。然而，特定的抗原的性质被推测地触发结节病的炎症反应，仍然难以捉摸。在空间相关的簇中发生结节病的发生，家庭和医疗保健环境强烈支持传染剂作为该疾病的潜在原因之一。结节病一直与多种传染剂有关，无法培养它们。痤疮（痤疮）和大结核病（MTB）是通过基于PCR的方法是最常见的传染病病原体（MTB），并被认为与该疾病的发展有关。结节病中的免疫学研究主要集中在患者和对照组中血液和肺部细胞表型的构成，免疫反应以及血液和肺细胞表型的描述上。在此提案中，我们将利用记忆免疫反应作为P.痤疮或MTB暴露的“免疫印记”的搜索工具。外周血单核细胞和支气管肺泡细胞将与患有II期和/或III期结节病的患者以及健康对照受试者进行比较。我们将通过ELISPOT测定法进行研究：（1）病原体特异性IFN-7和IL-10产生细胞的频率，以及（2）利用P.痤疮或MTB感染的自体型单核细胞和肺泡巨噬细胞作为病原体特异性格拉氏酶Breareal cytoxig cytoxik cytoxikic cytoxikic tlympocyt t lympoctocyt lymphocyt lymphocyt lymphocyt lymphocyt lymphocyt lymphocyt lymphocyt lymphocyt lymphocyt lymphocyt lymphocyt。最后，我们将测试通过DNA微阵列，病原体特异性，转录宿主基因表达谱鉴定的可行性，来自健康对照受试者和活性结节病的患者，并将其与自体的基因表达谱进行比较，并将其与自体的基因表达谱进行比较。我们的研究将解决痤疮和MTB在结节病的病因中的作用，还将作为未来工作的基础或模型，涉及其他可能的感染性或非感染性病原体/抗原来发展结节病。