PMID- 16088536
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20051006
LR  - 20050809
IS  - 1069-3424 (Print)
IS  - 1069-3424 (Linking)
VI  - 24
IP  - 2
DP  - 2003 Apr
TI  - Genetic factors modify the risk of developing beryllium disease.
PG  - 169-78
AB  - 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)-alpha 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-DPB1*0201 and TCRAV22S1/TCRBVb3 T cell receptors (TCRs) 
      confirmed beryllium specificity of these molecules. The G/A transition at -308 in 
      the TNF-alpha promoter was associated with high concentrations of TNF-alpha 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.
FAU - Tinkle, Sally S
AU  - Tinkle SS
AD  - Toxicology and Molecular Biology Branch, National Institute for Occupational 
      Safety and Health, Centers for Disease Control and Prevention, Morgantown, West 
      Virginia 26505, USA. sft3@cdc.gov
FAU - Weston, Ainsley
AU  - Weston A
FAU - Flint, Melanie S
AU  - Flint MS
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Semin Respir Crit Care Med
JT  - Seminars in respiratory and critical care medicine
JID - 9431858
EDAT- 2005/08/10 09:00
MHDA- 2005/08/10 09:01
CRDT- 2005/08/10 09:00
PHST- 2005/08/10 09:00 [pubmed]
PHST- 2005/08/10 09:01 [medline]
PHST- 2005/08/10 09:00 [entrez]
AID - 10.1055/s-2003-39016 [doi]
PST - ppublish
SO  - Semin Respir Crit Care Med. 2003 Apr;24(2):169-78. doi: 10.1055/s-2003-39016.