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Influence of MHC CLASS II in susceptibility to beryllium sensitization and chronic beryllium disease.

Authors
Maier-LA; McGrath-DS; Sato-H; Lympany-P; Welsh-K; Du Bois-R; Silveira-L; Fontenot-AP; Sawyer-RT; Wilcox-E; Newman-LS
Source
J Immunol 2003 Dec; 171(12):6910-6918
NIOSHTIC No.
20024240
Abstract
A glutamic acid at residue 69(Glu(69)) in the HLA-DPB1 gene (Glu(69)) is associated with chronic beryllium disease (CBD) and possibly beryllium sensitization (BeS). This study tested the hypothesis that MHC class II polymorphisms are important in susceptibility to BeS and CBD and that the Glu(69) variant is related to markers of disease severity. Genomic DNA was obtained from BeS (n = 50), CBD (n = 104), and beryllium-exposed nondiseased (Be-nondiseased) (n = 125) subjects. HLA-DPB1, -DRB1, and -DQB1 genotypes were determined by (sequence-specific primers) PCR. Disease severity was assessed by pulmonary function and exercise testing. A higher frequency of the DPB1 Glu(69) gene was found in CBD and BeS compared with the Be-nondiseased subjects, with odds ratios of 10.1 for CBD vs Be-nondiseased and 9.5 for BeS vs Be-nondiseased. The majority of BeS and CBD subjects displayed non-0201 Glu(69) alleles. Glu(69) homozygosity was higher in the CBD subjects, while BeS subjects were intermediate and Be-nondiseased lowest. DRB1*01 and DQB1*05 phenotypes were reduced in CBD vs Be-nondiseased subjects, while DRB1*13 and DQB1*06 were associated with CBD in the absence of Glu(69). Markers of disease severity, including a lower forced vital capacity, diffusion capacity for carbon monoxide, PaO(2) at rest, maximum workload on exercise testing, and a higher arterial-alveolar gradient at rest, were associated with Glu(69) homozygosity. We conclude that DPB1 Glu69 is a marker of sensitization and not specific for disease. Glu(69) homozygosity acts as a functional marker associated with markers of CBD severity.
Keywords
Beryllium-compounds; Beryllium-disease; Biological-agents; Biomarkers; Genes; Sensitivity-testing; Sensitization; Work-capacity; Respiration
Contact
National Jewish Medical and Research Center, Division of Environmental and Occupational Health Sciences, 1400 Jackson Street, Denver CO 80206
CODEN
JOIMA3
CAS No.
7440-41-7; 56-86-0
Publication Date
20031215
Document Type
Journal Article
Email Address
maierL@njc.org
Funding Amount
1980104
Funding Type
Cooperative Agreement
Fiscal Year
2004
NTIS Accession No.
NTIS Price
Identifying No.
Cooperative-Agreement-Number-U60-CCU-812221
Issue of Publication
12
ISSN
0022-1767
Source Name
The Journal of Immunology
State
CO
Performing Organization
National Jewish Medical and Research Center, Division of Environmental and Occupational Health Sciences, Denver Colorado 80206
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