Genetic Factors Modify the Risk of Developing Beryllium Disease

Details

• Personal Author:
  Flint MS ; Tinkle SS ; Weston A
• Description:
  Chronic beryllium disease (CBD) is a debilitating, granulomatous lung disease that occurs in 1 to 5% of exposed workers. Beryllium stimulates a major histocompatibility Class II-restricted, TH1, CD4+ T cell-mediated immune response. The immunological component of the illness, coupled with the small subset of beryllium workers who develop disease, led researchers to hypothesize that genetic factors modify risk of disease. Analysis of human leukocyte antigen (HLA) genes, the T cell receptor, and tumor necrosis factor (TNF)-a focused on three critical steps in the development of beryllium specific immunity. Molecular epidemiological analysis of the association of HLA-DP, -DR, and -DQ has implicated HLA-DPB1E69 allelic variants in disease; however, its role in sensitization is unclear. A single report suggested association between HLA-DQB1G86 and progression from sensitization to disease. A beryllium-specific binding motif was identified in CBD-derived T cell clones. Beryllium-stimulated proliferation using HLA-DPB110201 and TCRAV22S1/TCRBVb3 T cell receptors (TCRs) confirmed beryllium specificity of these molecules. The G/A transition at -308 in the TNF-a promoter was associated with high concentrations of TNF-a in bronchoalveolar lavage and to disease severity. Although these studies are continuing, the data confirm the role of genetic factors in the cellular response to beryllium. [Description provided by NIOSH]
• Subjects:
  Beryllium Lung Diseases Metals Metals, Heavy Occupational Health Poisoning Respiratory Tract Diseases Safety
• Keywords:
  Author Keywords: Beryllium Disease Beryllium-compounds Beryllium-disease Beryllium-poisoning Heavy-metal-poisoning Heavy-metals HLA Lung-disease Lung-disorders Pulmonary-system-disorders Respiratory-system-disorders Risk Factors T Cell Receptor TNF-alpha

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• ISSN:
  1069-3424
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  169-177
• Volume:
  24
• Issue:
  2
• NIOSHTIC Number:
  nn:20024164
• Citation:
  Semin Respir Crit Care Med 2003 Mar; 24(2):169-177
• CAS Registry Number:
  Beryllium (CAS RN 7440-41-7)
• Federal Fiscal Year:
  2003
• NORA Priority Area:
  Research Tools and Approaches: Risk Assessment Methods
• Peer Reviewed:
  True
• Source Full Name:
  Seminars in Respiratory and Critical Care Medicine
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8a62893408c10f8b132939a3807a0bf3cb46935cd9e9fc00130326c6f5586a7e53dbf76b3f856cff40e457f20e4f37b9e3649d446e40ea7353184b520224f664
• Download URL:
  https://stacks.cdc.gov/view/cdc/196126/cdc_196126_DS1.pdf
• File Type:
  [PDF - 5.31 MB ]