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）：机器工人的职业过敏性肺炎（HP）与经常定植于现代水基金属加工液（MWF）中的分枝杆菌有关。 HP 是一种由吸入微生物抗原引起的免疫介导的肺部疾病，其诊断、发病机制和治疗方面的研究相对较少。本研究的总体目标是鉴定和表征与 MWF 分枝杆菌种 M.immunogenum (MI) 和 M.chelonae (MC) HP 诱导潜力相关的抗原，并评估它们用于 HP 免疫诊断和暴露评估的潜力。在之前的资助周期中，我们分离出了两个具有可变抗原特征的物种的多个菌株（基因型）。我们将检验我们的假设，即商业 MWF 中普遍存在的 MWF 分枝杆菌菌株的抗原多样性负责差异性诱导 HP 症状和潜在的免疫反应，并且负责的特定抗原可以构成提供更多信息的诊断以及个人和环境暴露评估的基础。具体目标是：（1）．根据优化的 HP 小鼠模型中 MI 和 MC 品系与宿主免疫系统的相对相互作用，识别 MI 和 MC 品系中的关键抗原； （2）。通过克隆和蛋白表达重组生产已鉴定的关键抗原并产生特异性抗体； （3）。研究特定抗原在有症状与无症状个体中进行早期个人暴露评估和免疫诊断的潜力； （4）。评估 MWF 分枝杆菌特定抗原用于环境暴露评估（液体监测）的潜力。将使用我们优化的小鼠模型，根据 HP 诱导潜力和细胞介导的免疫反应，比较分离的不同基因型 MI (6) 和 MC (4) 的相对免疫原性，并通过差异免疫蛋白质组分析来鉴定推定的蛋白质抗原。将使用小鼠模型和人类受试者评估重组表达的抗原的免疫诊断潜力，特别是在区分无症状（暴露）与有症状（HP患者）以及环境暴露评估方面。由此产生的信息将通过提供一套用于分枝杆菌暴露评估和 HP 免疫诊断的工具来帮助 NORA 实现目标；这些结果将有助于未来的流行病学研究以及针对小金属加工液长期接触的预防（疫苗接种）和干预策略的制定。 公共健康相关性：现代金属加工液 (MWF) 中定植的非结核分枝杆菌 (NTM) 与职业性呼吸道疾病有关。 NIOSH 和其他团体最近的研究表明，金属加工液分枝杆菌与接触机器工人的职业性过敏性肺炎 (HP) 存在关联。 HP 是一种由吸入微生物抗原引起的免疫介导的肺部疾病。因此，MWF 分枝杆菌中特定抗原的表征以及对其 HP 免疫诊断和暴露评估潜力的评估将有助于在 MWF 相关职业环境中制定先发制人的措施和干预策略。