The beryllium lymphocyte proliferation test: Relevant issues in beryllium health surveillance

Stange, Arthur W.; Furman, F. Joseph; Hilmas, Duane E.

doi:10.1002/ajim.20082

Cited by 70 publications

(94 citation statements)

References 32 publications

(32 reference statements)

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“…The findings of that initial study were confirmed in larger studies [3] and by different investigators [4,5]. Around 10 yrs later, an immunological test (the beryllium lymphocyte proliferation test (BeLPT)) was initially used in cross-sectional studies and later in the surveillance and screening of current and former beryllium workers [6][7][8]. Those studies demonstrated that CBD was not heading for the medical archives, but that the disease was present in much greater numbers than previously reported due to misdiagnosis of overt cases and the detection of early and asymptomatic cases through immunological testing.…”

supporting

confidence: 48%

Justification for screening for chronic beryllium disease: closer to reality

Rossman¹

2008

Eur Respir J

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supporting

confidence: 48%

Justification for screening for chronic beryllium disease: closer to reality

Rossman¹

2008

Eur Respir J

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“…The presence of a beryllium-specific immune response in blood is detected by the beryllium lymphocyte proliferation test (BeLPT) (11)(12)(13). This assay is used for screening and diagnosis of beryllium sensitization in the workplace and is a required component of the US Department of Energy CBD prevention program (23).…”

Section: Figurementioning

confidence: 99%

“…Beryllium sensitization is associated with the presence of circulating beryllium-specific CD4 + T cells, which proliferate in the presence of beryllium salts in culture in an MHC class II-restricted manner (6)(7)(8)(9)(10). The in vitro response forms the basis of the beryllium lymphocyte proliferation test (BeLPT), which is currently used to detect beryllium sensitization in the workplace (11)(12)(13). Progression from sensitization to CBD occurs at a rate of 6-8% per year (14) and is characterized by the accumulation of large numbers of berylliumspecific, Th1-type cytokine-secreting CD4 + T cells in the lung and granulomatous inflammation.…”

Section: Introductionmentioning

confidence: 99%

Frequency of beryllium-specific, central memory CD4+ T cells in blood determines proliferative response

Fontenot

Palmer²,

Sullivan³

et al. 2005

Journal of Clinical Investigation

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Beryllium exposure can lead to the development of beryllium-specific CD4 + T cells and chronic beryllium disease (CBD), which is characterized by the presence of lung granulomas and a CD4 + T cell alveolitis. Studies have documented the presence of proliferating and cytokine-secreting CD4 + T cells in blood of CBD patients after beryllium stimulation. However, some patients were noted to have cytokine-secreting CD4 + T cells in blood in the absence of beryllium-induced proliferation, and overall, the correlation between the 2 types of responses was poor. We hypothesized that the relative proportion of memory T cell subsets determined antigen-specific proliferation. In most CBD patients, the majority of beryllium-specific CD4 + T cells in blood expressed an effector memory T cell maturation phenotype. However, the ability of blood cells to proliferate in the presence of beryllium strongly correlated with the fraction expressing a central memory T cell phenotype. In addition, we found a direct correlation between the percentage of beryllium-specific CD4 + T EM cells in blood and T cell lymphocytosis in the lung. Together, these findings indicate that the functional capability of antigen-specific CD4 + T cells is determined by the relative proportion of memory T cell subsets, which may reflect internal organ involvement. IntroductionWith a known antigen and an accessible target organ, chronic beryllium disease (CBD) serves as an important model of an organ-specific immune-mediated disease. This disorder occurs in susceptible individuals exposed to beryllium in the workplace, and more than 1 million workers are at risk for the development of CBD (1-5). Beryllium sensitization is associated with the presence of circulating beryllium-specific CD4 + T cells, which proliferate in the presence of beryllium salts in culture in an MHC class II-restricted manner (6-10). The in vitro response forms the basis of the beryllium lymphocyte proliferation test (BeLPT), which is currently used to detect beryllium sensitization in the workplace (11-13). Progression from sensitization to CBD occurs at a rate of 6-8% per year (14) and is characterized by the accumulation of large numbers of berylliumspecific, Th1-type cytokine-secreting CD4 + T cells in the lung and granulomatous inflammation. Important differences exist between antigen-specific T cells that reside in the lung and those present in the circulation. For example, beryllium-specific memory CD4 + T cells in blood remain dependent on CD28 engagement for optimal T cell activation, while the memory CD4 + T cells present in bronchoalveolar lavage (BAL) no longer require CD28 costimulation for either proliferation or Th1-type cytokine secretion; this suggests a maturation within the memory CD4 + T cell population (15).Using ELISPOT analysis, we found significant numbers of IFN-γ-secreting CD4 + T cells when peripheral blood cells from CBD

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“…Stange et al reported a false positive rate of nearly 2% and a false negative rate of 32%. 35 All medical screening tests can have false positive or false negative results. A second, confirmatory abnormal BeLPT result is often required for a person to be considered sensitized to beryllium.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of a Program to Prevent Beryllium Sensitization among New Employees at a Copper-Beryllium Alloy Processing Facility

et al. 2009

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SYNOPSISObjectives. In 2000, 7% of workers at a copper-beryllium facility were beryllium sensitized. Risk was associated with work near a wire annealing/pickling process. The facility then implemented a preventive program including particle migration control, respiratory and dermal protection, and process enclosure. We assessed the program's efficacy in preventing beryllium sensitization.Methods. In 2000, the facility began testing new hires (program workers) with beryllium lymphocyte proliferation tests (BeLPTs) at hire and at intervals during employment. We compared sensitization incidence rates (IRs) and prevalence rates for workers hired before the program (legacy workers) with rates for program workers, including program worker subgroups. We also examined trends in BeLPTs from a single laboratory.Results. In all, five of 43 legacy workers (IR53.8/1,000 person-months) and three of 82 program workers (IR51.9/1,000 person-months) were beryllium sensitized, for an incidence rate ratio (IRR) of 2.0 (95% confidence interval [CI] 0.5, 10.1). Two of 37 pre-enclosure program workers (IR52.4/1,000 person-months) and one of 45 post-enclosure program workers (IR51.4/1,000 person-months) were beryllium sensitized, for IRRs of 1.6 (95% CI 0.3, 11.9) and 2.8 (95% CI 0.4, 66.2), respectively, compared with legacy workers. Test for trend in prevalence rates was significant. Among 2,159 first-draw BeLPTs during 95 months, we identified seven months when high numbers of redraws were required, with one possible misclassification in this facility.Conclusions. Fewer workers became sensitized after implementation of the preventive program. However, low statistical power due to the facility's small workforce prevents a definitive conclusion about the program's efficacy. These findings have implications for other copper-beryllium facilities, where program components may merit application.

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The beryllium lymphocyte proliferation test: Relevant issues in beryllium health surveillance

Abstract: The Be-LPT is efficacious in medical surveillance of beryllium-exposed individuals. The PPV of the Be-LPT is comparable to other widely accepted medical tests. Confirmation of an abnormal result is recommended to assure appropriate referral for CBD medical evaluation.

Cited by 70 publications

References 32 publications

Justification for screening for chronic beryllium disease: closer to reality

Justification for screening for chronic beryllium disease: closer to reality

Frequency of beryllium-specific, central memory CD4+ T cells in blood determines proliferative response

Efficacy of a Program to Prevent Beryllium Sensitization among New Employees at a Copper-Beryllium Alloy Processing Facility

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