Major histocompatibility locus genetic markers of beryllium sensitization and disease
Major histocompatibility locus genetic markers of beryllium sensitization and disease
Hypersensitivity to beryllium (Be) is found in 1-16% of exposed workers undergoing immunological screening for beryllium disease using the beryllium lymphocyte proliferation test (BeLPT). However, only approximately 50% of BeLPT-positive workers present with lung granulomas (i.e. berylliosis). As berylliosis is associated with the human leukocyte antigen (HLA)-DP supratypic marker DPGlu69, the authors asked whether this marker is differentially associated with disease presentation. A population of 639 workers from a beryllium factory undergoing BeLPT screening was evaluated in a nested case-control study for the prevalence of HLA-DPGlu69, the HLA-DPB1, HLA-DQ and HLA-DR alleles and of the biallelic tumour necrosis factor (TNF)-alpha polymorphism TNF-alpha-308 in 23 individuals presenting as "sensitized" (i.e. BeLPT-positive without lung granulomas) and in 22 presenting as "diseased" (i.e. BeLPT-positive with granulomas in the lung biopsy). The HLA-DPGlu69 marker was associated with "disease" (odds ratio (OR) 3.7, p=0.016, 95% confidence interval (CI) 1.4-10.0), whilst the high TNF-alpha production-related TNF-alpha-308*2 marker was associated with both a positive BeLPT (OR 7.8, corrected p<0.0001, 95% CI 3.2-19.1) with no difference between "sensitization" and "disease". Furthermore, the HLA-DRArg74 marker was associated with "sensitization" without disease (OR 3.96, p=0.005, 95%, CI 1.5-10.1). The data indicate that tumour necrosis factor-alpha, human leukocyte antigen-DR and human leukocyte antigen-DP markers play different roles in beryllium sensitization and granuloma formation in beryllium-exposed workers.
berylliosis, genetic susceptibility, human leukocyte antigen-DPGlu69, human leukocyte antigen-DR, tumour necrosis factor-a
677-684
Saltini, C.
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Richeldi, L.
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Losi, M.
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Amicosante, M.
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Voorter, C.
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van den Berg-Loonen, E.
5dbd3b6f-0cd5-4f6e-a3fc-776760b6da18
Dweik, R. A.
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Wiedemann, H. P.
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Deubner, D. C.
653806b3-c7ba-4c6c-ba2e-442cba823aba
Tinelli, C.
5496e9f9-98df-4e23-b315-c2423c718582
1 October 2001
Saltini, C.
511217a8-2901-4ca3-bbdf-b54611e4acc2
Richeldi, L.
c4dea37c-7aec-4487-8512-da2f6a3c045e
Losi, M.
5d48476e-5760-47eb-bd74-573132186a06
Amicosante, M.
deeb6cc8-e796-4c25-8e92-6b79000d737c
Voorter, C.
610dbadf-d29a-4a4e-9546-d833d0118411
van den Berg-Loonen, E.
5dbd3b6f-0cd5-4f6e-a3fc-776760b6da18
Dweik, R. A.
fcf9f119-0dca-4ab2-84fc-13a561df8810
Wiedemann, H. P.
591a3a50-0056-47bd-a3db-4ffe061744d2
Deubner, D. C.
653806b3-c7ba-4c6c-ba2e-442cba823aba
Tinelli, C.
5496e9f9-98df-4e23-b315-c2423c718582
Saltini, C., Richeldi, L., Losi, M., Amicosante, M., Voorter, C., van den Berg-Loonen, E., Dweik, R. A., Wiedemann, H. P., Deubner, D. C. and Tinelli, C.
(2001)
Major histocompatibility locus genetic markers of beryllium sensitization and disease.
European Respiratory Journal, 18 (4), .
(PMID:11716174)
Abstract
Hypersensitivity to beryllium (Be) is found in 1-16% of exposed workers undergoing immunological screening for beryllium disease using the beryllium lymphocyte proliferation test (BeLPT). However, only approximately 50% of BeLPT-positive workers present with lung granulomas (i.e. berylliosis). As berylliosis is associated with the human leukocyte antigen (HLA)-DP supratypic marker DPGlu69, the authors asked whether this marker is differentially associated with disease presentation. A population of 639 workers from a beryllium factory undergoing BeLPT screening was evaluated in a nested case-control study for the prevalence of HLA-DPGlu69, the HLA-DPB1, HLA-DQ and HLA-DR alleles and of the biallelic tumour necrosis factor (TNF)-alpha polymorphism TNF-alpha-308 in 23 individuals presenting as "sensitized" (i.e. BeLPT-positive without lung granulomas) and in 22 presenting as "diseased" (i.e. BeLPT-positive with granulomas in the lung biopsy). The HLA-DPGlu69 marker was associated with "disease" (odds ratio (OR) 3.7, p=0.016, 95% confidence interval (CI) 1.4-10.0), whilst the high TNF-alpha production-related TNF-alpha-308*2 marker was associated with both a positive BeLPT (OR 7.8, corrected p<0.0001, 95% CI 3.2-19.1) with no difference between "sensitization" and "disease". Furthermore, the HLA-DRArg74 marker was associated with "sensitization" without disease (OR 3.96, p=0.005, 95%, CI 1.5-10.1). The data indicate that tumour necrosis factor-alpha, human leukocyte antigen-DR and human leukocyte antigen-DP markers play different roles in beryllium sensitization and granuloma formation in beryllium-exposed workers.
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Published date: 1 October 2001
Keywords:
berylliosis, genetic susceptibility, human leukocyte antigen-DPGlu69, human leukocyte antigen-DR, tumour necrosis factor-a
Organisations:
Clinical & Experimental Sciences
Identifiers
Local EPrints ID: 368939
URI: http://eprints.soton.ac.uk/id/eprint/368939
ISSN: 0903-1936
PURE UUID: 03d6d147-f4bc-4ddc-8a96-ba8044bd8d46
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Date deposited: 02 Oct 2014 13:30
Last modified: 22 Jul 2022 19:08
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Contributors
Author:
C. Saltini
Author:
L. Richeldi
Author:
M. Losi
Author:
M. Amicosante
Author:
C. Voorter
Author:
E. van den Berg-Loonen
Author:
R. A. Dweik
Author:
H. P. Wiedemann
Author:
D. C. Deubner
Author:
C. Tinelli
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