Eur Respir J 2001; 18:677-684
Copyright ©ERS Journals Ltd 2001
Major histocompatibility locus genetic markers of beryllium sensitization and disease
C. Saltini1,
L. Richeldi2,
M. Losi2,
M. Amicosante3,
C. Voorter4,
E. van den Berg-Loonen4,
R.A. Dweik5,
H.P. Wiedemann5,
D.C. Deubner6 and
C. Tinelli7
1 Division of Respiratory Diseases of the University of Rome "Tor Vergata" at the National Institute for Infectious Diseases (INMI), Spallanzani Hospital, Rome, Italy. 2 Division of Pneumology, Policlinico, Modena, Italy. 3 Laboratory of Clinical Pathology, INMI, Spallanzani Hospital, and the Dept of Cell Biology, University of "Tor Vergata", Rome, Italy. 4 Tissue Typing Laboratory, University Hospital Maastricht, Maastricht, the Netherlands. 5 Pulmonary and Intensive Care, Cleveland Clinic Foundation, Cleveland, OH, USA. 6 Medical Dept, Brush Wellman Inc., Elmore, OH, USA. 7 Biostatistics Unit, IRCCS San Matteo, Pavia, Italy
CORRESPONDENCE: C. Saltini, Divisione di Malattie Respiratorie, Ospedale L. Spallanzani-I.R.C.C.S., via Portuense, 292 00149, Roma, Italy. Fax: 39 0655170413
Keywords: berylliosis, genetic susceptibility, human leukocyte antigen-DPGlu69, human leukocyte antigen-DR, tumour necrosis factor-;
Received: December 12, 2000
Accepted June 10, 2001
This work was supported by grants DE-FG02-93ER61714 and ER61714-1004058 0000196 from the Dept of Energy of the USA and grant 99060855594 from MURST, Italy.
Hypersensitivity to beryllium (Be) is found in 116% of exposed workers undergoing immunological screening for beryllium disease using the beryllium lymphocyte proliferation test (BeLPT). However, only 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)-; polymorphism TNF-; -;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) 1.410.0), whilst the high TNF-; production-related TNF-; -;308*2 marker was associated with both a positive BeLPT (OR 7.8, corrected p<0.0001, 95% CI 3.219.1) 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 1.510.1).
The data indicate that tumour necrosis factor-; , 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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Copyright © 2001 by the European Respiratory Society.
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