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Published on: November 1, 2015
Beryllium sensitivity is linked to HLA-DP genotype.
Z Wang1, G M Farris, L S Newman
1B-2, M888, Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
Toxicology
|September 12, 2001
Summary
Genetic variations in the HLA-DPB1 gene, specifically the Glu69 substitution, are linked to beryllium hypersensitivity. This finding provides direct evidence of HLA-DP genotype
Area of Science:
- Immunogenetics
- Occupational Medicine
- Pulmonary Medicine
Background:
- Chronic beryllium disease (CBD) results from beryllium exposure and genetic factors.
- Beryllium hypersensitivity, a precursor to CBD, is characterized by lymphocyte proliferation upon beryllium exposure.
- Specific HLA-DPB1 gene variations have been previously associated with CBD.
Purpose of the Study:
- To investigate the association between HLA-DPB1 allelic variations and beryllium hypersensitivity in individuals without clinical CBD.
- To determine if specific HLA-DPB1 genotypes are present in beryllium-sensitive individuals who have not developed CBD.
Main Methods:
- A flow cytometry-based Lymphocyte Proliferation Test with immunophenotyping (Immuno-LPT) was employed to measure CD4+ and CD8+ T cell responses to beryllium.
- HLA-DPB1 haplotypes were analyzed using automated DNA sequencing in beryllium-sensitive, non-CBD individuals.
- T cell proliferation patterns were correlated with specific HLA-DPB1 genotypes.
Main Results:
- Twenty-two of 25 beryllium-sensitive, non-CBD individuals carried the HLA-DPB1 gene with a glutamic acid substitution at position 69 in Exon 2 (Glu69).
- A significant percentage (24%) of these individuals were Glu69 homozygotes.
- CD4+ T cell responders predominantly carried rare, non-*0201 Glu69 DPB1 alleles, whereas non-CD4+ responders were common Glu69 carriers or non-Glu69 individuals.
Conclusions:
- This study provides the first direct evidence linking HLA-DP genotype to the phenotypic response of beryllium sensitization.
- The presence of specific HLA-DPB1 variations, particularly Glu69, is associated with beryllium hypersensitivity independent of clinical CBD development.
- These findings highlight the role of immunogenetic factors in the early stages of beryllium-related diseases.
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