title: Major histocompatibility locus genetic markers of beryllium sensitization and disease.
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.
authors.affiliation: Division of Respiratory Diseases of the University of Rome Tor Vergata at the National Institute for Infectious Diseases, Spallanzani Hospital, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Saltini
authors.forename: L
authors.initials: L
authors.lastname: Richeldi
authors.forename: M
authors.initials: M
authors.lastname: Losi
authors.forename: M
authors.initials: M
authors.lastname: Amicosante
authors.forename: C
authors.initials: C
authors.lastname: Voorter
authors.forename: E
authors.initials: E
authors.lastname: van den Berg-Loonen
authors.forename: R A
authors.initials: RA
authors.lastname: Dweik
authors.forename: H P
authors.initials: HP
authors.lastname: Wiedemann
authors.forename: D C
authors.initials: DC
authors.lastname: Deubner
authors.forename: C
authors.initials: C
authors.lastname: Tinelli
mesh_terms: D000328:Adult; D001607:Berylliosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D001608:Beryllium / Q000009:adverse effects* / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006682:HLA-DP Antigens / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology / Q000235:genetics*; D008168:Lung / Q000473:pathology; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D005819:Genetic Markers; D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D014409:Tumor Necrosis Factor-alpha; D001608:Beryllium