The natural history of beryllium sensitization and chronic beryllium disease.

Newman, Lee S.; Lloyd, Jenifer; Daniloff, Elaine

doi:10.1289/ehp.96104s5937

Cited by 79 publications

(53 citation statements)

References 16 publications

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“…The pathology of CBD is identical to that seen in sarcoidosis, a more common granulomatous lung disease of unknown etiology (13). Due to the persistence of Be in the lung years after exposure cessation (14), the natural history of disease is characterized by a gradual decline in lung function, with one-third of untreated patients historically progressing to end-stage respiratory insufficiency (15). …”

Section: Introductionmentioning

confidence: 99%

Beryllium-Induced Hypersensitivity: Genetic Susceptibility and Neoantigen Generation

Fontenot

Falta

Kappler

et al. 2016

The Journal of Immunology

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Chronic beryllium disease (CBD) is a granulomatous lung disorder that results from beryllium (Be) exposure in a genetically-susceptible host. The disease is characterized by the accumulation of Be-responsive CD4+ T cells in the lung, and genetic susceptibility is primarily linked to HLA-DPB1 alleles possessing a glutamic acid at position 69 of the β-chain. Recent structural analysis of a Be-specific T cell receptor (TCR) interacting with a Be-loaded HLA-DP2-peptide complex revealed that Be is coordinated by amino acid residues derived from the HLA-DP2 β-chain and peptide and showed that the TCR does not directly interact with the Be2+ cation. Rather, the TCR recognizes a modified HLA-DP2-peptide complex with charge and conformational changes. Collectively, these findings provide a structural basis for the development of this occupational lung disease through the ability of Be to induce post-translational modifications in preexisting HLA-DP2-peptide complexes, resulting in the creation of neoantigens.

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Section: Introductionmentioning

confidence: 99%

Beryllium-Induced Hypersensitivity: Genetic Susceptibility and Neoantigen Generation

Fontenot

Falta

Kappler

et al. 2016

The Journal of Immunology

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“…Chronic beryllium disease (CBD) is an immunologic lung disease caused by inhalation of beryllium dust and fume (1). Exposed workers can develop beryllium sensitization (BeS), a beryllium-specific, cell-mediated immune response, which is measured by the beryllium lymphocyte proliferation test (BeLPT) (2–5).…”

mentioning

confidence: 99%

Chronic Beryllium Disease, HLA-DPB1, and the DP Peptide Binding Groove

Silveira

McCanlies

Fingerlin

et al. 2012

The Journal of Immunology

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Multiple epidemiologic studies demonstrate associations between chronic beryllium disease (CBD), beryllium sensitization (BeS), and HLA-DPB1 alleles with a glutamic acid residue at position 69 (E69). Results suggest that the less-frequent E69 variants (non-*0201/*0202 alleles) might be associated with greater risk of CBD. In this study, we sought to define specific E69-carrying alleles and their amino acid sequences in the DP peptide binding groove, as well as their relationship to CBD and BeS risk, using the largest case control study to date. We enrolled 502 BeS/CBD subjects and 653 beryllium-exposed controls from three beryllium industries who gave informed consent for participation. Non-Hispanic white cases and controls were frequency-matched by industry. HLA-DPB1 genotypes were determined using sequence-specific primer PCR. The E69 alleles were tested for association with disease individually and grouped by amino acid structure using logistic regression. The results show that CBD cases were more likely than controls to carry a non-*02 E69 allele than an *02 E69, with odds ratios (95% confidence interval) ranging from 3.1 (2.1–4.5) to 3.9 (2.6–5.9) (p < 0.0001). Polymorphic amino acids at positions 84 and 11 were associated with CBD: DD versus GG, 2.8 (1.8–4.6), p < 0.0001; GD versus GG, 2.1 (1.5–2.8), p < 0.0001; LL versus GG, 3.2 (1.8–5.6), p < 0.0001; GL versus GG, 2.8 (2.1–3.8), p < 0.0001. Similar results were found within the BeS group and CBD/BeS combined group. We conclude that the less frequent E69 alleles confer more risk for CBD than does *0201. Recent studies examining how the composition and structure of the binding pockets influence peptide binding in MHC genes, as well of studies showing the topology of the TCR to likely bind DPB1 preferentially, give plausible biological rationale for these findings.

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“…CBD is characterized by the presence of noncapsulating granulomatous inflammation in the lung and subsequent development of progressive fibrosis 16 . Accumulating evidence clearly suggests that CBD is recognized as an immune-mediated granulomatous reaction.…”

Section: Berylliummentioning

confidence: 99%

Pulmonary Fibrosis in Response to Environmental Cues and Molecular Targets Involved in Its Pathogenesis

et al. 2011

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Chronic lung injury resulting from a variety of different causes is frequently associated with the develop ment of pulmonary fibrosis in humans. Although the etiology of pulmonary fibrosis is generally unknown, several sources of evidence support the hypothesis that a number of environmental and occupational agents play an etiologic role in the pathogenesis of this disease. The agents discussed in this review include beryllium, nylon flock, textile printing aerosols, polyvinyl chloride and didecyldimethylammonium chloride. The authors also describe a variety of animal models, including genetically modified mice, in order to investigate the molecular mechanism of pulmonary fibrosis, focusing on chemokine receptors, regulatory T cells and transforming growth factor-β and bone morphogenetic protein signaling. Overall, we propose the concept of toxicological pulmonary fibrosis as a lung disease induced in response to environmental cues.

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The natural history of beryllium sensitization and chronic beryllium disease.

Cited by 79 publications

References 16 publications

Beryllium-Induced Hypersensitivity: Genetic Susceptibility and Neoantigen Generation

Beryllium-Induced Hypersensitivity: Genetic Susceptibility and Neoantigen Generation

Chronic Beryllium Disease, HLA-DPB1, and the DP Peptide Binding Groove

Pulmonary Fibrosis in Response to Environmental Cues and Molecular Targets Involved in Its Pathogenesis

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