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: 7886344
• 负责人: Jagjit S Yadav
• 金额: $ 39.99万
• 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/7886344
• 关键词: MWF; Mycobacteria; antigens; occupational; hypersensitivity

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Non-tuberculous mycobacteria (NTM) colonizing modern metalworking fluids (MWFs) have been associated with occupational respiratory illnesses. Recent studies by NIOSH and other groups have linked MWF mycobacteria with occupational hypersensitivity pneumonitis (HP) in exposed machine workers. HP is an immune-mediated lung disease caused by inhalation of microbial antigens. Hence, characterization of specific antigens in MWF mycobacteria and evaluation of their potential for HP immunodiagnosis and exposure assessment will facilitate development of pre-emptive measures and intervention strategies in MWF-associated occupational environments.

描述（由申请人提供）：机械工人中的职业超敏性肺炎（HP）与经常定居现代水基金属加工液（MWFS）有关。 HP是一种由微生物抗原吸入引起的免疫介导的肺疾病，就其诊断，发病机理和治疗而言，研究相对较差。这项研究的总体目标是识别和表征与MWF分枝杆菌种植菌M.免疫原（MI）和M. chelonae（MC）相关的抗原，并评估其HP免疫诊断和暴露评估的潜力。在以前的资金周期中，我们具有具有可变抗原特性的两个物种的多种菌株（基因型）。我们将检验我们的假设，即商业MWF中普遍存在的MWF分枝杆菌菌株中的抗原多样性负责差异化HP症状和潜在的免疫反应，并且负责任的特定抗原可以为更具信息性的诊断和个人和环境暴露评估构成基础。具体目的是：（1）。根据优化的HP小鼠模型，基于其与宿主免疫系统的相对相互作用来识别MI和MC菌株中的关键抗原； （2）。通过克隆和蛋白质表达以及特定抗体的产生来重组鉴定的关键抗原； （3）。研究特异性抗原在症状性和无症状个体中对早期个人暴露评估和免疫诊断的潜力； （4）。评估MWF分枝杆菌的特异性抗原对环境暴露评估（流体监测）的潜力。使用我们优化的小鼠模型，将根据HP诱导潜力和细胞介导的免疫反应进行比较的分离的MI和MC（4）不同基因型的相对免疫原性，并通过优化的蛋白质抗原通过差异免疫蛋白质分析来鉴定推定的蛋白质抗原。重组表达的抗原将使用小鼠模型和人类受试者进行免疫诊断的潜力，尤其是在无症状（暴露）（暴露）与症状性（HP患者）和环境暴露评估方面的潜力。最终的信息将通过提供一组用于分枝杆菌暴露评估和HP免疫诊断的工具来帮助NORA的目标；这些结果将促进未来的流行病学研究和预防的发展（疫苗接种）和MWF长期暴露的干预策略。 公共卫生相关性：非结核分枝杆菌（NTM）定居现代金属加工液（MWF）与职业呼吸道疾病有关。 NIOSH和其他小组的最新研究将MWF分枝杆菌与暴露的机器工人中的职业性超敏性肺炎（HP）联系起来。 HP是一种由微生物抗原吸入引起的免疫介导的肺疾病。因此，对MWF分枝杆菌中特定抗原的表征以及其对HP免疫诊断的潜力和暴露评估的评估将有助于发展与MWF相关的职业环境中的先发制人措施和干预策略。