Immunogenetics Factors in Chronic Beryllium Disease

Details

• Personal Author:
  Demchuk, Eugene ; Kreiss, Kathleen ; McCanlies E ; Schuler C ; Snyder J ; Weston A
• Description:
  Exposure to beryllium in the workplace can cause beryllium sensitization and chronic beryllium disease. Sensitization to beryllium can be detected in the laboratory using a beryllium lymphocyte proliferation test. It was shown that anti-HLA antibodies could block the beryllium specific response in the beryllium lymphocyte proliferation test, thereby implicating HLA-genes in chronic beryllium disease. A supratypic genetic marker, HLA-DPBIE69, has been shown to be strongly associated with immunologic sensitization to beryllium and chronic beryllium disease in beryllium workers. Among the 36 HLA-DPB1 gene variants that code for E69, molecular epidemiological studies have suggested a risk hierarchy; where some variants appear to convey low to moderate risk (e.g., HLA-DPB1*0201, approximately 2-fold), some convey an intermediate risk (e.g., HLA-DPBl*1901, approximately 5-fold) and others convey high risk (e.g., HLA-DPBl*1701, > l0-fold). Computational chemistry has been used to further investigate a potential mechanistic basis for these observations. A strong correlation has been found between the hierarchical order of risk of chronic beryllium disease associated with specific alleles and the predicted surface electrostatic potential of the corresponding isotypes. This approach has further been used to predict the binding affinities of different residues for positivety charged beryllium ions in different HLA-DPB1 molecules. These findings suggest that preferential cation binding to specific HLA amino acid sequences in a putatively metal-free antigen-binding pocket might selectively alter the innate specificity of antigen recognition. In addition, it may be possible to use a computational chemistry approach to identify candidate susceptibility genes for further investigation of occupational diseases. [Description provided by NIOSH]
• Subjects:
  Beryllium Hypersensitivity Laboratories Occupational Diseases Occupational Exposure Occupational Health Risk Assessment Risk Factors Safety
• Keywords:
  Beryllium-disease Diseases Laboratory-testing Occupational-diseases Occupational-exposure Risk-analysis Risk-factors Sensitization Worker-health Workers
• ISSN:
  0278-0240
• 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 ; DRDS - Division of Respiratory Disease Studies
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  7
• Volume:
  20
• Issue:
  1
• NIOSHTIC Number:
  nn:20030940
• Citation:
  Dis Markers 2004 Jan; 20(1):7
• Federal Fiscal Year:
  2004
• Peer Reviewed:
  True
• Source Full Name:
  Disease Markers
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:64184657b728502dba1cae4b32336d521ee668aa9034b988027b0e3d3cdca972a0908a00e52b2933f08f9a55a547086fd4f2fb92767599d452082a5dc4a7eb83
• Download URL:
  https://stacks.cdc.gov/view/cdc/191367/cdc_191367_DS1.pdf
• File Type:
  [PDF - 428.83 KB ]