Optimizing BeLPT criteria for beryllium sensitization

Middleton, Dan; Fink, J.N.; Kowalski, Peter; Lewin, Michael; Sinks, Thomas

doi:10.1002/ajim.20548

Cited by 23 publications

(34 citation statements)

References 11 publications

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“…This argument has been primarily based on the reports of variable intra-and inter-laboratory reproducibility of the test [Deubner et al, 2001;Stange et al, 2004]. The current consensus is for sensitization to be confirmed by either a second abnormal test or borderline result [Welch et al, 2004;Middleton et al, 2008; National Research Council of the National Academies, 2008].…”

Section: Discussionmentioning

confidence: 99%

“…At 3-5 years from the initial screening all participating workers with an initial normal result were offered a repeat BeLPT. Beryllium sensitization was defined as either two abnormal BeLPTs, or one abnormal and one borderline test [US DOE, 2001;Welch et al, 2004;Middleton et al, 2008]. No restrictions were placed on whether these results were produced by the same lab or by different laboratories.…”

Section: Screening For Beryllium Sensitization and Abnormal Lung Physmentioning

confidence: 99%

See 1 more Smart Citation

Risk of beryllium sensitization in a low‐exposed former nuclear weapons cohort from the cold war era

Mikulski

Leonard

Sanderson

et al. 2010

American J Industrial Med

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Section: Discussionmentioning

confidence: 99%

Section: Screening For Beryllium Sensitization and Abnormal Lung Physmentioning

confidence: 99%

Risk of beryllium sensitization in a low‐exposed former nuclear weapons cohort from the cold war era

Mikulski

Leonard

Sanderson

et al. 2010

American J Industrial Med

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“…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)(3)(4)(5). Once workers develop BeS, they may subsequently develop CBD, a diffuse lung disease characterized by granulomatous inflammation in the lung.…”

mentioning

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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“…In an effort to clarify the interpretation of a positive BeLPT and what constitutes BeH, Middleton et al [8 ] sought to compare the performance of three criteria proposed by experts who were convened by the Agency for Toxic Substances and Disease Registry in 2006. Using probability algorithms the authors concluded that a single unconfirmed abnormal test is usually insufficient to establish sensitization except when used in a high prevalence group.…”

Section: Occupational Exposure Limits and Preventive Measuresmentioning

confidence: 99%