{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:57:39Z","timestamp":1774616259431,"version":"3.50.1"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2001,10,1]],"date-time":"2001-10-01T00:00:00Z","timestamp":1001894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Beryllium (Be)-antigen stimulates tumor necrosis factor-alpha (TNF- \u03b1) from bronchoalveolar lavage (BAL) cells in chronic beryllium disease (CBD). This study tested the hypothesis that high concentrations of Be-stimulated TNF- \u03b1 are related to polymorphisms in the TNF- \u03b1 promoter and clinical markers of disease severity in CBD. Demographic and clinical information was obtained from patients with CBD (n = 20). TNF- \u03b1 concentrations were measured in BAL cell culture supernatant by ELISA. A priori, we categorized CBD subjects as either high or low TNF- \u03b1 producers using a cutoff of 1,500 pg\/ml. The TNF- \u03b1 promoter sequence, + 64 to \u2212 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- \u03b1 was associated with TNF2 alleles, Hispanic ethnicity, presence of HLA-DPB1 Glu69, and absence of HLA-DR4. Be-stimulated TNF- \u03b1 concentrations correlated with markers of disease severity, including chest radiograph, beryllium lymphocyte proliferation, and spirometry. We found no novel TNF- \u03b1 promoter polymorphisms. These data suggest that the TNF2 A allele at \u2212 308 in the TNF- \u03b1 promoter region is a functional polymorphism, associated with a high level of Be-antigen-stimulated TNF- \u03b1 and that these high TNF- \u03b1 levels indicate disease severity in CBD.<\/jats:p>","DOI":"10.1164\/ajrccm.164.7.2012123","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T14:54:06Z","timestamp":1365087246000},"page":"1192-1199","source":"Crossref","is-referenced-by-count":48,"title":["High Beryllium-stimulated TNF- \u03b1 Is Associated with the \u2212 308 TNF- \u03b1 Promoter Polymorphism and with Clinical Severity in Chronic Beryllium Disease"],"prefix":"10.1093","volume":"164","author":[{"given":"LISA A.","family":"MAIER","sequence":"first","affiliation":[{"name":"Division of Environmental and Occupational Health Sciences, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado; Division of Pulmonary Science and Critical Care Medicine, Department of Medicine, and Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colorado; and Interstitial Lung Disease Unit, Department of Occupational and Environmental Medicine, Imperial College of Science, Technology and Medicine, National Heart and Lung Institute, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"RICHARD T.","family":"SAWYER","sequence":"additional","affiliation":[{"name":"Division of Environmental and Occupational Health Sciences, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado; Division of Pulmonary Science and Critical Care Medicine, Department of Medicine, and Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colorado; and Interstitial Lung Disease Unit, Department of Occupational and Environmental Medicine, Imperial College of Science, Technology and Medicine, National Heart and Lung Institute, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ROSLYN A.","family":"BAUER","sequence":"additional","affiliation":[{"name":"Division of Environmental and Occupational Health Sciences, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado; Division of Pulmonary Science and Critical Care Medicine, Department of Medicine, and Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colorado; and Interstitial Lung Disease Unit, Department of Occupational and Environmental Medicine, Imperial College of Science, Technology and Medicine, National Heart and Lung Institute, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"LORI A.","family":"KITTLE","sequence":"additional","affiliation":[{"name":"Division of Environmental and Occupational Health Sciences, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado; Division of Pulmonary Science and Critical Care Medicine, Department of Medicine, and Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colorado; and Interstitial Lung Disease Unit, Department of Occupational and Environmental Medicine, Imperial College of Science, Technology and Medicine, National Heart and Lung Institute, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"PENNY","family":"LYMPANY","sequence":"additional","affiliation":[{"name":"Division of Environmental and Occupational Health Sciences, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado; Division of Pulmonary Science and Critical Care Medicine, Department of Medicine, and Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colorado; and Interstitial Lung Disease Unit, Department of Occupational and Environmental Medicine, Imperial College of Science, Technology and Medicine, National Heart and Lung Institute, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"DEIRDRE","family":"McGRATH","sequence":"additional","affiliation":[{"name":"Division of Environmental and Occupational Health Sciences, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado; Division of Pulmonary Science and Critical Care Medicine, Department of Medicine, and Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colorado; and Interstitial Lung Disease Unit, Department of Occupational and Environmental Medicine, Imperial College of Science, Technology and Medicine, National Heart and Lung Institute, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ROLAND","family":"DUBOIS","sequence":"additional","affiliation":[{"name":"Division of Environmental and Occupational Health Sciences, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado; Division of Pulmonary Science and Critical Care Medicine, Department of Medicine, and Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colorado; and Interstitial Lung Disease Unit, Department of Occupational and Environmental Medicine, Imperial College of Science, Technology and Medicine, National Heart and Lung Institute, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ELAINE","family":"DANILOFF","sequence":"additional","affiliation":[{"name":"Division of Environmental and Occupational Health Sciences, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado; Division of Pulmonary Science and Critical Care Medicine, Department of Medicine, and Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colorado; and Interstitial Lung Disease Unit, Department of Occupational and Environmental Medicine, Imperial College of Science, Technology and Medicine, National Heart and Lung Institute, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"CECILE S.","family":"ROSE","sequence":"additional","affiliation":[{"name":"Division of Environmental and Occupational Health Sciences, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado; Division of Pulmonary Science and Critical Care Medicine, Department of Medicine, and Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colorado; and Interstitial Lung Disease Unit, Department of Occupational and Environmental Medicine, Imperial College of Science, Technology and Medicine, National Heart and Lung Institute, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"LEE 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