MWF Mycobacteria antigens in occupational hypersensitivity pneumonitis

MWF 职业性过敏性肺炎中的分枝杆菌抗原

• 批准号: 8301478
• 负责人: Jagjit S Yadav
• 金额: $ 38.28万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8301478
• 关键词: MWF; Mycobacteria; antigens; occupational; hypersensitivity

Project summary Occupational hypersensitivity pneumonitis (HP) in machine workers has been associated with mycobacteria that frequently colonize modern water-based metalworking fluids (MWFs). HP is an immune-mediated lung disease caused by inhalation of microbial antigens and is relatively poorly studied in terms of its diagnosis, pathogenesis, and treatment. Overall goal of this study is to identify and characterize antigens associated with HP-inducing potential of MWF mycobacteria species M. immunogenum (MI) and M. chelonae (MC) and evaluate their potential for HP immunodiagnosis and exposure assessment. In previous funding cycles, we have isolated multiple strains (genotypes) of both the species with variable antigenic characteristics. We will test our hypothesis that antigen diversity in MWF mycobacteria strains prevalent in commercial MWF is responsible for differentially inducing the HP symptoms and underlying immune response, and that the responsible specific antigens could form the basis for more informative diagnosis and personal and environmental exposure assessment. The specific aims are to: (1). Identify key antigens in MI and MC strains based on their relative interaction with the host immune system in an optimized mouse model of HP; (2). Recombinant production of the identified key antigens by cloning and protein expression and generation of specific antibodies; (3). Investigate potential of the specific antigens for early personal exposure assessment and immunodiagnosis in symptomatic versus asymptomatic individuals; (4). Evaluate potential of the specific antigen(s) of MWF mycobacteria for environmental exposure assessment (fluid monitoring). Relative immunogenicity of the isolated different genotypes of MI (6) and MC (4) will be compared based on HP induction potential and cell-mediated immune response using our optimized mouse model and the putative protein antigens will be identified by differential immunoproteomic profiling. The recombinantly expressed antigens will be evaluated for their potential for immunodiagnosis using the mouse model and human subjects, particularly in terms of differentiation of the asymptomatic (exposed) versus symptomatic (HP patients) and for environmental exposure assessment. The resulting information will help NORA's objectives by providing a set of tools for mycobacterial exposure assessment and HP immunodiagnosis; these outcomes will facilitate future epidemiological studies and development of prevention (vaccination) and intervention strategies for MWF exposures in long-term.

项目摘要 机器工人的职业超敏性肺炎（HP）已经是 与经常定居现代水基金属加工的分枝杆菌相关 流体（MWF）。 HP是一种免疫介导的肺疾病 微生物抗原，就其诊断，发病机理而言，研究相对较差 和治疗。这项研究的总体目标是识别和表征抗原 与MWF分枝杆菌的诱导HP诱导潜力有关。 （MI）和M. chelonae（MC），并评估其HP免疫诊断的潜力和 暴露评估。在以前的资金周期中，我们有多种菌株 具有可变抗原特性的两个物种的（基因型）。我们将测试我们的 假设MWF分枝杆菌菌株中普遍存在的抗原多样性在商业中普遍存在 MWF负责差异诱导HP症状和潜在的免疫 反应，并且负责任的特定抗原可以构成更多的基础 内容丰富的诊断以及个人和环境暴露评估。这 具体目标是：（1）。根据它们的MI和MC菌株中的密钥抗原 在优化的HP小鼠模型中，与宿主免疫系统的相对相互作用； （2）。通过克隆和蛋白质重组产生鉴定的关键抗原 特定抗体的表达和产生； （3）。调查特定的潜力 抗原早期个人暴露评估和有症状的免疫诊断 相对于无症状的个体； （4）。评估特定抗原的潜力 MWF分枝杆菌环境暴露评估（流体监测）。相对的 分离的不同基因型MI（6）和MC（4）的免疫原性将为 根据HP诱导电位和细胞介导的免疫反应进行比较 我们优化的小鼠模型和推定的蛋白质抗原将通过 差异免疫蛋白质分析。重组表达的抗原将是 评估使用小鼠模型和人类的免疫诊断潜力 受试者，特别是在无症状（暴露）与 有症状的（HP患者）和环境暴露评估。结果 信息将通过提供分生不清的工具来帮助NORA的目标 暴露评估和HP免疫诊断；这些结果将促进未来 流行病学研究和预防的发展（疫苗接种）和干预 长期接触MWF的策略。