Chronic beryllium disease, HLA-DPB1, and the DP peptide binding groove

Details

• Personal Author:
  Bowerman N ; Dabelea DM ; Fingerlin TE ; Fontenot AP ; Maier LA ; McCanlies EC ; Mroz MM ; Schuler, Christine R. ; Silveira LJ ; Strand M ; Van Dyke MV ; Weston A
• Description:
  Multiple epidemiologic studies demonstrate associations between chronic beryllium disease (CBD), beryllium sensitization (BeS), and HLA-DPB1 alleles with a glutamic acid residue at position 69 (E69). Results suggest that the less-frequent E69 variants (non-*0201/*0202 alleles) might be associated with greater risk of CBD. In this study, we sought to define specific E69-carrying alleles and their amino acid sequences in the DP peptide binding groove, as well as their relationship to CBD and BeS risk, using the largest case control study to date. We enrolled 502 BeS/CBD subjects and 653 beryllium-exposed controls from three beryllium industries who gave informed consent for participation. Non-Hispanic white cases and controls were frequency-matched by industry. HLA-DPB1 genotypes were determined using sequence-specific primer PCR. The E69 alleles were tested for association with disease individually and grouped by amino acid structure using logistic regression. The results show that CBD cases were more likely than controls to carry a non-*02 E69 allele than an *02 E69, with odds ratios (95% confidence interval) ranging from 3.1 (2.1-4.5) to 3.9 (2.6-5.9) (p < 0.0001). Polymorphic amino acids at positions 84 and 11 were associated with CBD: DD versus GG, 2.8 (1.8-4.6), p < 0.0001; GD versus GG, 2.1 (1.5-2.8), p < 0.0001; LL versus GG, 3.2 (1.8-5.6), p < 0.0001; GL versus GG, 2.8 (2.1-3.8), p < 0.0001. Similar results were found within the BeS group and CBD/BeS combined group. We conclude that the less frequent E69 alleles confer more risk for CBD than does *0201. Recent studies examining how the composition and structure of the binding pockets influence peptide binding in MHC genes, as well of studies showing the topology of the TCR to likely bind DPB1 preferentially, give plausible biological rationale for these findings. [Description provided by NIOSH]
• Subjects:
  Acids Amino Acids Beryllium Case Reports Epidemiology Genetics Hypersensitivity Occupational Health Risk Assessment Risk Factors Safety

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• Keywords:
  Amino-acids Beryllium-compounds Beryllium-disease Case-studies Genes Genetic-factors Glutamates Peptides Risk-analysis Risk-factors Sensitization

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• ISSN:
  0022-1767
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Colorado ; OSHA Region 3 ; OSHA Region 8 ; 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
• Volume:
  189
• Issue:
  8
• NIOSHTIC Number:
  nn:20041803
• Citation:
  J Immunol 2012 Oct; 189(8):4014-4023
• Contact Point Address:
  Dr. Lori J. Silveira, National Jewish Health, 1400 Jackson, Denver, CO 80206
• Email:
  silveiral@njhealth.org
• CAS Registry Number:
  Beryllium (CAS RN 7440-41-7) ; L-Glutamic acid (CAS RN 56-86-0)
• Federal Fiscal Year:
  2013
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  The Journal of Immunology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:2357a79a5732c3a908a9806a48e0c20691eb1a2ada57b4bcccfe50e33ed88bcccac5ea995f0ee600d4d31d2892f1ebfa192bae15f3216b3c162f68ba642d3204
• Download URL:
  https://stacks.cdc.gov/view/cdc/194260/cdc_194260_DS1.pdf
• File Type:
  [PDF - 1.19 MB ]