Document Detail

Chronic beryllium disease, HLA-DPB1, and the DP peptide binding groove.
MedLine Citation:
PMID:  22972925     Owner:  NLM     Status:  MEDLINE    
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.
Lori J Silveira; Erin C McCanlies; Tasha E Fingerlin; Michael V Van Dyke; Margaret M Mroz; Matthew Strand; Andrew P Fontenot; Natalie Bowerman; Dana M Dabelea; Christine R Schuler; Ainsley Weston; Lisa A Maier
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2012-09-12
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  189     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-08     Completed Date:  2012-12-18     Revised Date:  2013-01-23    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4014-23     Citation Subset:  AIM; IM    
National Jewish Health, Denver, CO 80206, USA.
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MeSH Terms
Amino Acid Substitution / drug effects,  genetics,  immunology
Berylliosis / genetics,  immunology*,  pathology
Beryllium / adverse effects,  chemistry*
Case-Control Studies
Chronic Disease
HLA-DP beta-Chains / chemistry*,  genetics
Inflammation Mediators / adverse effects,  chemistry
Polymorphism, Genetic / immunology
Protein Binding / drug effects,  genetics,  immunology
Respiratory Hypersensitivity / genetics,  immunology,  pathology
Static Electricity
Grant Support
Reg. No./Substance:
0/HLA-DP beta-Chains; 0/HLA-DPB1 antigen; 0/Inflammation Mediators; 7440-41-7/Beryllium

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