The association between <i>HLA‐DPB1<sup>Glu69</sup></i> and chronic beryllium disease and beryllium sensitization

McCanlies, Erin C.; Ensey, James; Schuler, Christine R.; Kreiss, Kathleen; Weston, Ainsley

doi:10.1002/ajim.20045

Cited by 75 publications

(76 citation statements)

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“…The genetic basis of immunologic reactivity to beryllium involves human leukocyte antigens (HLA); the beryllium-induced proliferation of T lymphocytes from lungs of chronic beryllium disease patients was blocked by antibodies directed against the DP subgroup of HLA (16,54). Many studies have shown that HLA-DP alleles having a glutamic acid in the sixty-ninth position of the B1 chain of this molecule confer higher risk of chronic beryllium disease and sensitization (36,38,48,49,51,53,71,72). Such HLA-DPB1…”

Section: Geneticsmentioning

confidence: 99%

“…In one study of three beryllium facilities, 4% of the participants had two copies of the HLA-DPB1 Glu69 marker (homozygous) and 29% had one copy (heterozygous); the risk of chronic beryllium disease to the former was three times greater than the risk to the latter (38). Among the 119 known HLA-DPB1 alleles, the 42 alleles with glutamic acid in the sixty-ninth position can be divided into subsets that fall into a risk hierarchy.…”

Section: Geneticsmentioning

confidence: 99%

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Beryllium: A Modern Industrial Hazard

Kreiss

Day²,

Schuler³

2007

Annu. Rev. Public Health

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Beryllium exposure can cause a granulomatous lung disease in workers who develop a lymphocyte-mediated sensitization to the metal. Workers in diverse industries are at risk because beryllium's properties are critical to nuclear, aerospace, telecommunications, electronic, metal alloy, biomedical, and semiconductor industries. The occupational air concentration standard's failure to protect beryllium workers is driving many scientific and occupational health advances. These developments include study of bioavailability of different physicochemical forms of beryllium, medical surveillance to show effectiveness of skin protection in preventing sensitization in high-risk processes, gene-environment interaction, transgenic mice for use in experimental research, and risk-based management of industrial exposures in the absence of effective exposure-response information. Beryllium sensitization and disease prevention are paradigms for much broader public health action in both occupational and general population settings.

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Section: Geneticsmentioning

confidence: 99%

Section: Geneticsmentioning

confidence: 99%

Beryllium: A Modern Industrial Hazard

Kreiss

Day²,

Schuler³

2007

Annu. Rev. Public Health

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“…The investigators theorized that the shape of the peptide binding groove offers a possible explanation for how beryllium can access the glutamic acid at this position, resulting in T cell activation. Questions still persist regarding other aspects of the HLA structure that might be equally (or even more) powerful in allowing beryllium access to the peptide binding groove.With the ongoing investigation into the relative relationships between specific HLA-DPB1 alleles and risk of CBD (7,8,(10)(11)(12)(13)(14), the main objective of this study was to evaluate the associations between specific HLA-DPB1 alleles and the presence or absence of CBD utilizing the largest number of cases and controls to date. We hypothesized that the risk of CBD would be higher in specific lower E69 frequency alleles (non-*02) and that these less frequent alleles (LFAs) would have similar amino acid configurations in the peptide binding groove in this region.…”

mentioning

confidence: 99%

“…Only ~2-10% of exposed workers develop BeS or CBD, and there has been a lack of a clear linear exposure response relationship noted in most, but not all, studies to date (7)(8)(9). This observation has led researchers to investigate genetic factors that might increase the risk of disease and sensitization.…”

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confidence: 99%

Chronic Beryllium Disease, HLA DPB1 And The DP Peptide Binding Groove

Silveira¹,

McCanlies²,

Fingerlin³

et al. 2011

C54. Hypersensitivity Pneumonitis and Berylliosis

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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 frequencymatched 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.Copyright © 2012 by The American Association of Immunologists, Inc.Address correspondence and reprint requests to: Dr. Lori J. Silveira, National Jewish Health, 1400 Jackson, Denver, CO 80206. silveiral@njhealth.org. DisclosuresThe authors have no financial conflicts of interest. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptChronic 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). Once workers develop BeS, they may subsequently develop CBD, a diffuse lung disease characterized by granulomatous inflammation in the lung. Differentiation between CBD and BeS is determined by performing a clinical evaluation consisting of a lung biopsy and bronchoalveolar lavage. BeS precedes CBD, and it is estimated that between 3 and 9% (6) of those who are sensitized progress to disease each year. Beryllium exposure is necessary for sensitization and disease, but not all who are exposed develop sensitization and not all ...

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“…Blood samples were analyzed for the well known lysine (K)/glutamic acid (E) polymorphism at position 69 of the HLA-DPβ1 gene. This was done by fractionating the blood and isolating the white blood cells, extracting DNA, amplifying the target gene (HLA-DPβ1), and identifying the coding sequence at position 69 [McCanlies et al 2004].…”

Section: Genetic Analysesmentioning

confidence: 99%

Health hazard evaluation report: HETA-2003-0257-3088, report on respiratory symptoms and disease among cemented tungsten carbide workers, Metalworking Products, Huntsville, Gurley, and Grant, Alabama.

2009

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This Health Hazard Evaluation (HHE) report and any recommendations made herein are for the specific facility evaluated and may not be universally applicable. Any recommendations made are not to be considered as final statements of NIOSH policy or of any agency or individual involved. Additional HHE reports are available at http://www.cdc.gov/niosh/hhe/ The employer shall post a copy of this report for a period of 30 calendar days at or near the workplace(s) of affected employees. The employer shall take steps to insure that the posted determinations are not altered, defaced, or covered by other material during such period.

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The association between HLA‐DPB1^Glu69 and chronic beryllium disease and beryllium sensitization

Abstract: Follow-up of this cohort, scrutiny of HLA-DPB1 haplotypes, and evaluation of gene-environment and gene-gene interactions will be important for fully understanding the immunogenetic nature of this occupational disease.

Cited by 75 publications

References 25 publications

Beryllium: A Modern Industrial Hazard

Beryllium: A Modern Industrial Hazard

Chronic Beryllium Disease, HLA DPB1 And The DP Peptide Binding Groove

Health hazard evaluation report: HETA-2003-0257-3088, report on respiratory symptoms and disease among cemented tungsten carbide workers, Metalworking Products, Huntsville, Gurley, and Grant, Alabama.

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The association between HLA‐DPB1Glu69 and chronic beryllium disease and beryllium sensitization

Abstract: Follow-up of this cohort, scrutiny of HLA-DPB1 haplotypes, and evaluation of gene-environment and gene-gene interactions will be important for fully understanding the immunogenetic nature of this occupational disease.

Cited by 75 publications

References 25 publications

Beryllium: A Modern Industrial Hazard

Beryllium: A Modern Industrial Hazard

Chronic Beryllium Disease, HLA DPB1 And The DP Peptide Binding Groove

Health hazard evaluation report: HETA-2003-0257-3088, report on respiratory symptoms and disease among cemented tungsten carbide workers, Metalworking Products, Huntsville, Gurley, and Grant, Alabama.

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The association between HLA‐DPB1^Glu69 and chronic beryllium disease and beryllium sensitization