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Beryllium (Be)-antigen stimulates tumor necrosis factor-alpha (TNF- α ) from bronchoalveolar lavage (BAL) cells in chronic beryllium disease (CBD). This study tested the hypothesis that high concentrations of Be-stimulated TNF- α are related to polymorphisms in the TNF- α promoter and clinical markers of disease severity in CBD. Demographic and clinical information was obtained from patients with CBD (n = 20). TNF- α concentrations were measured in BAL cell culture supernatant by ELISA. A priori, we categorized CBD subjects as either high or low TNF- α producers using a cutoff of 1,500 pg/ml. The TNF- α promoter sequence, + 64 to − 1045, was determined by direct sequencing. Human leukocyte-associated antigen (HLA)-DPB1 and -DRB1 genotyping was determined by polymerase chain reaction (PCR). High Be-stimulated TNF- α was associated with TNF2 alleles, Hispanic ethnicity, presence of …