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Genetic factors modify the risk of developing beryllium disease.

Authors
Tinkle-SS; Weston-A; Flint-MS
Source
Semin Respir Crit Care Med 2003 Mar; 24(2):169-177
NIOSHTIC No.
20024164
Abstract
Chronic beryllium disease (CBD) is a debilitating, granulomatous lung disease that occurs in 1 to 5% of exposed workers. Beryllium stimulates a major histocompatibility Class II-restricted, TH1, CD4+ T cell-mediated immune response. The immunological component of the illness, coupled with the small subset of beryllium workers who develop disease, led researchers to hypothesize that genetic factors modify risk of disease. Analysis of human leukocyte antigen (HLA) genes, the T cell receptor, and tumor necrosis factor (TNF)-a focused on three critical steps in the development of beryllium specific immunity. Molecular epidemiological analysis of the association of HLA-DP, -DR, and -DQ has implicated HLA-DPB1E69 allelic variants in disease; however, its role in sensitization is unclear. A single report suggested association between HLA-DQB1G86 and progression from sensitization to disease. A beryllium-specific binding motif was identified in CBD-derived T cell clones. Beryllium-stimulated proliferation using HLA-DPB110201 and TCRAV22S1/TCRBVb3 T cell receptors (TCRs) confirmed beryllium specificity of these molecules. The G/A transition at -308 in the TNF-a promoter was associated with high concentrations of TNF-a in bronchoalveolar lavage and to disease severity. Although these studies are continuing, the data confirm the role of genetic factors in the cellular response to beryllium.
Keywords
Beryllium-compounds; Beryllium-disease; Beryllium-poisoning; Heavy-metal-poisoning; Heavy-metals; Respiratory-system-disorders; Pulmonary-system-disorders; Lung-disease; Lung-disorders
CODEN
SRCCEX
CAS No.
7440-41-7
Publication Date
20030301
Document Type
Journal Article
Fiscal Year
2003
NTIS Accession No.
NTIS Price
Issue of Publication
2
ISSN
1069-3424
NIOSH Division
HELD
Priority Area
Research Tools and Approaches: Risk Assessment Methods
Source Name
Seminars in Respiratory and Critical Care Medicine
State
WV
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