RT Journal Article
SR Electronic
T1 Major histocompatibility locus genetic markers of beryllium sensitization and disease
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 677
OP 684
DO 10.1183/09031936.01.00106201
VO 18
IS 4
A1 C. Saltini
A1 L. Richeldi
A1 M. Losi
A1 M. Amicosante
A1 C. Voorter
A1 E. van den Berg-Loonen
A1 R.A. Dweik
A1 H.P. Wiedemann
A1 D.C. Deubner
A1 C. Tinelli
YR 2001
UL http://erj.ersjournals.com/content/18/4/677.abstract
AB 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 ∼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)-;α polymorphism TNF-;α-;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-;α production-related TNF-;α-;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-;α, human leukocyte antigen-DR and human leukocyte antigen-DP markers play different roles in beryllium sensitization and granuloma formation in beryllium-exposed workers.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.