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Beryllium lymphocyte proliferation test

Beryllium is an alkaline earth metal that is alloyed with copper, aluminum and nickel and used in a number of different industrial applications. People working in machine shops, electronics, defense industry, and beryllium extraction facilities have the highest exposure to beryllium. People employed in automotive, ceramic, computer, aerospace, metal reclamation, electronics and computer recycling, jewelry making, and dental alloy/appliance businesses may also be exposed.

Chronic beryllium disease, or berylliosis, is a granulomatous disease caused by exposure to beryllium. A patient is considered to have CBD if all of the following are present:

  • A history of any beryllium exposure
  • A positive blood or bronchoalveolar lavage (BAL) beryllium lymphocyte proliferation test (BeLPT)
  • Noncaseating granulomas and/or mononuclear cell infiltrates on lung biopsy

A patient is considered to have beryllium sensitization when they have a positive BeLPT performed on blood or BAL mononuclear cells, but no detectable lung pathology.

The blood BeLPT is the most appropriate initial test for patients suspected of having CBD. It has become the standard industry surveillance tool for identifying workers who have become beryllium-sensitized or developed early disease. Repeated testing is recommended for monitoring employees with ongoing exposure.

In the BeLPT assay, mononuclear cells from peripheral blood or bronchoalveolar lavage (BAL) are exposed in vitro to three different concentrations of beryllium salts (eg, beryllium sulfate) for two different time intervals. Cell proliferation is measured by the incorporation of tritiated thymidine into the DNA of dividing cells. The cutoff value for a positive test is laboratory-dependent. If none of the six resultant tests show increased lymphocyte proliferation, the test is normal. If one of the six incubations shows increased uptake, the test is interpreted to be borderline. If two or more of the incubations show increased uptake the test is abnormal. The specificity of in vitro generated beryllium-reactive cells can be demonstrated by the lack of response to other metals and by the normal stimulation index of those exposed to beryllium without evidence of disease.

Sensitivity of a single peripheral blood BeLPT is 0.683 and specificity 0.96. To improve sensitivity and resolve borderline test results, all negative and borderline tests are generally repeated. If the second test is either positive or borderline, the patient is considered to be sensitized to beryllium. Among patients with a positive blood BeLPT, 20 to 100 percent will have evidence of CBD based on BAL or transbronchial biopsy results. This wide range has been attributed to variations in the magnitude of beryllium exposure in the workplace.

Because of the low sensitivity, a patient may still have CBC even if the initial and repeat BeLPT tests are negative. Thus, for an individual with clinical evidence of lung disease and a history of exposure to beryllium, even at very low levels, further testing for CBD (eg, bronchoalveolar lavage, tissue biopsy) would be indicated even if the blood BeLPT is negative.

References

Balmes JR, Abraham JL, Dweik RA, et al. An official American Thoracic Society statement: diagnosis and management of beryllium sensitivity and chronic beryllium disease. Am J Respir Crit Care Med 2014; 190:e34.

Newman LS, Kreiss K. Nonoccupational beryllium disease masquerading as sarcoidosis: identification by blood lymphocyte proliferative response to beryllium. Am Rev Respir Dis 1992; 145:1212.

Kreiss K, Miller F, Newman LS, et al. Chronic beryllium disease--from the workplace to cellular immunology, molecular immunogenetics, and back. Clin Immunol Immunopathol 1994; 71:123.

Middleton D, Kowalski P. Advances in identifying beryllium sensitization and disease. Int J Environ Res Public Health 2010; 7:115.

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