MWF Mycobacteria Antigens in Occupational Hypersensitivity Pneumonitis

Details

• Personal Author:
  Lockey J ; Succop P ; Yadav JS
• Description:
  Hypersensitivity pneumonitis (HP) in machine workers, commonly called 'Machine Operator's Lung', is a well-recognized occupational lung disease in machinists. Studies by NIOSH and others have associated this disease with exposure to mycobacteria which frequently colonize modern water-based metalworking fluids (MWFs) used in machining. This is an immune-mediated lung disease caused due to repeated inhalational exposure to microbial antigens; HP is difficult to diagnose due to lack of clinical diagnosis tools and its pathogenesis, and treatment are poorly studied. Considering this, overall goal of this study was to identify and characterize specific antigens from our collection of industrial MWF-isolated mycobacteria [M. immunogenum (MI), M. chelonae (MC), and M. abscessus (MA)] and evaluate their potential for use in HP diagnosis and exposure assessment. In this context, we tested our hypothesis that antigen diversity in MWF mycobacteria species/strains prevalent in commercial MWF is responsible for differentially inducing HP symptoms and the underlying immune response, and that the responsible specific antigens could form the basis for more informative immunodiagnosis and exposure assessment. Relative immunogenicity of twelve MWF-isolated mycobacteria strains belonging to the three species was compared based on HP induction potential and cell-mediated immune response using our optimized mouse models of experimental HP. A repertoire of antigen candidates (both secreted and cell-associated) was identified from different MWF mycobacteria genotypes by differential immunoproteomic profiling. Selected key antigen candidates were recombinantly expressed and purified and evaluated for their potential for HP immunodiagnosis using the developed mouse model and human subjects. Use of human blood and serum samples from machinists and healthy control subjects led to identification of mycobacterial antigens that were selectively seroreactive with the patient samples. Further evaluation of the recombinant antigens for ex-vivo T-cell reactivity using lymphocytes isolated from HP mouse models and HP patients (machinists) led to identification of a pair of potent bivalent antigen candidates (which were both sero-reactive and T cell-reactive). Additional efforts led to optimization of an immune-PCR assay for sensitive detection of mycobacterial antigen in MWF for exposure assessment applications. The specific antigens in MWF mycobacteria identified and characterized in this study will facilitate future epidemiological studies and development of intervention strategies for MWF antigen exposures and incidence of this immune lung disease in machinists. Overall, the resulting information will help NORA's objectives by providing a set of tools for developing applications for differential clinical diagnosis of machinists HP and exposure assessment; these outcomes could also facilitate development of pre-emptive measures and intervention strategies in occupational machining environments in long-term. [Description provided by NIOSH]
• Subjects:
  Animals Antigens Immune System Inhalation Exposure Lung Diseases Manufacturing And Industrial Facilities Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  Animal Studies Exposure Assessment Hypersensitivity Pneumonitis Immune Reaction Inhalants Lung Disease Machine Operators Machinists Metalworking Fluids MWFs Mycobacterium

  More +
• Series:
  Grant Final Reports
• Publisher:
  National Institute for Occupational Safety and Health
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Final Grant Report
• Place as Subject:
  Ohio ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  OEP - Office of Extramural Programs
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  1-27
• NIOSHTIC Number:
  nn:20052368
• NTIS Accession Number:
  PB2018-101425
• Citation:
  Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, R01-OH-007364, 2017 Nov; :1-27
• Contact Point Address:
  Jagjit S. Yadav, Ph.D, Professor, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0056
• Email:
  Jagjit.Yadav@uc.edu
• Federal Fiscal Year:
  2018
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Cincinnati
• Peer Reviewed:
  False
• Start Date:
  20010930
• Source Full Name:
  National Institute for Occupational Safety and Health
• End Date:
  20170731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:01e116cb61f9da8155a12c2544805f0236677f097f4b6ca9605da6a9ea707ed7e1894b53a64faaca5cde98719ade96096ff928f20559a887e86134a9b8718432
• Download URL:
  https://stacks.cdc.gov/view/cdc/218702/cdc_218702_DS1.pdf
• File Type:
  [PDF - 1.15 MB ]