Immunogenetic Factors in Beryllium Sensitization and Chronic Beryllium Disease

Details

• Personal Author:
  Andrew, Michael E. ; Demchuk, Eugene ; Kreiss, Kathleen ; McCanlies EC ; Schuler, Christine R. ; 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 the 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-DPB1*E69, was found to be strongly associated with immunologic sensitization to beryllium and chronic beryllium disease in beryllium workers. However, there are 40 HLA-DPB1 gene variants that have E69 but that also have other DNA sequence variations. The purpose of the study was to evaluate the evidence for potential differential susceptibility that may be associated with the physical characteristics of HLA protein molecules for which different HLA-DPB1*E69 variants code; that is, do some HLA-DPB1*E69 variants convey higher risk of beryllium sensitization and chronic beryllium disease than others. To do this, two approaches were pursued: first, detailed analysis of the findings from the published literature was performed, and second, computational chemistry was used to seek clues concerning the physical properties of the HLA protein molecules for which these alleles code. Among the 40 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 of chronic beryllium disease (e.g., HLA-DPB1*0201, approximately 3-fold increased risk), some convey an intermediate risk (e.g., HLA-DPB1*1901, approximately 5-fold) and others convey high risk (e.g., HLA-DPB1*1701, >10-fold). Molecular modeling has been used to further investigate a potential mechanistic basis for these observations. We found a strong correlation between the hierarchical order of risk of chronic beryllium disease associated with specific alleles and the predicted surface electrostatic potential and charge of the corresponding isotypes. Therefore, when alleles were grouped by the relative negative charge on the molecules for which they code, the data suggest that those alleles associated with the most negatively charged proteins carry the greatest risk of beryllium sensitization and disease. [Description provided by NIOSH]
• Subjects:
  Beryllium Biomarkers Epidemiology Hypersensitivity Laboratories Occupational Diseases Occupational Exposure Occupational Health Risk Assessment Risk Factors Safety

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• Keywords:
  Beryllium-compounds Diseases Laboratory-testing Occupational-diseases Occupational-exposure Risk-analysis Risk-factors Sensitization Workers
• ISSN:
  0027-5107
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DRDS - Division of Respiratory Disease Studies ; HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  68-78
• Volume:
  592
• Issue:
  1
• NIOSHTIC Number:
  nn:20028892
• Citation:
  Mutat Res 2005 Dec; 592(1-2):68-78
• Contact Point Address:
  Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Mailstop L-3014, Morgantown, WV 26505-2888, USA
• Email:
  agw8@cdc.gov
• CAS Registry Number:
  Beryllium (CAS RN 7440-41-7)
• Federal Fiscal Year:
  2006
• Peer Reviewed:
  True
• Source Full Name:
  Mutation Research
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:06fdd2aadbc35831da6a6c3246b25956412f77663b8dda93b734017ef0b1058f816d055fb09d089643b1f6c3f732c2b5c527a510ec1428e065c3b899ee5ac61e
• Download URL:
  https://stacks.cdc.gov/view/cdc/189988/cdc_189988_DS1.pdf
• File Type:
  [PDF - 372.17 KB ]