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Major histocompatibility locus genetic markers of beryllium sensitization and disease

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
0903-1936
677-684
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.
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), 677-684. (PMID:11716174)

Record type: Article

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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More information

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

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Local EPrints ID: 368939
URI: https://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: 18 Jul 2017 01:41

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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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