Beryllium lymphocyte

Maier LA. Beryllium health effects in the era of the beryllium lymphocyte proliferation test. Appl Occup Environ Hyg 2001 16 514-20. 

Beryllium exposure has been studied in 3185 workers from nine aluminium smelters owned by four different aluminium-producing companies, of whom 1932 workers participated in medical surveillance programs that included the serum beryllium lymphocyte proliferation test, confirmation of sensitization by at least two abnormal test results, and further evaluation for chronic beryllium disease in workers with beryllium sensitivity [41 ]. Nine workers had beryllium sensitivity (prevalence rate = 0.47%, 95% CI = 0.21, 0.88). The authors attributed the low rate of sensitization in aluminium smelters to the more soluble form of beryllium found in the aluminium smelting work environment and the consistent use of respiratory protection. 

Newman LS. Significance of the blood beryllium lymphocyte proliferation test. Environ Health Perspect 1996 104(suppl 5) 953-956. 

Stange AW, Furman FJ, Hilmas DE. The beryllium lymphocyte proliferation test relevant issues in berylhum health surveillance. Am J Ind Med 2004 46(5) ... 

Johannson L, Albin M, Jakobsson K, Mikoczy Z (1992) Histological type of lung carcinoma in asbestos cement workers and matched controls. Br J Indust Med 49 626-630 Jones WW, Williams WR (1983) Value of beryllium lymphocyte transformation tests in chronic beryllium disease and in potentially exposed workers. Thorax 38 41-44 Jones RN, Hughes JM, Weill H (1996) Asbestos exposure, asbestosis, and asbestos-attributable lung cancer. Thorax 51 [Suppl2] 59-515... 

Barna BP, Culver DA, Yen-Lieberman B et al (2003) Clinical application of beryllium lymphocyte proliferation testing. Clin Diagn Lab Immunol 990-994 Baur X, Richter G, Pethran A et al (1992) Increased prevalence of IgG-induced sensitization and hypersensitivity pneumonitis (humidifier lung) in nonsmokers exposed to aerosols of a contaminated air conditioner. Respiration 59 211-214... 

Frome EL, Newman LS, Cragle DL et al (2003) Identification of an abnormal beryllium lymphocyte proliferation test. Toxicology 183 39-56... 

Williams WR, Williams WJ (1982) Development of beryllium lymphocyte transformation in chronic beryllium disease. Int Arch Allergy Appl Immunol 67 175-180... 

An immunologic basis for chronic beryllium disease has been postulated and a hypersensitivity phenomenon demonstrated. Consistent with the concept of chronic berylliosis as a hypersensitivity pulmonary reaction are the following Persons with berylliosis also show delayed cutaneous hypersensitivity reactions to beryllium compounds their peripheral blood lymphocytes undergo blast transformation and release of macrophage inhibition factor after exposure to beryllium in vitro helper/suppressor T-cell ratios are depressed and there is lack of a dose-response relationship in chronic beryllium cases. Hypersensitization may lead to berylliosis in people with relatively low exposures, whereas nonsensitized individuals with higher exposures may have no effects. 

Impairment of the immune response has also been demonstrated with beryllium in experimental animals (136). The long latency period associated with berylliosis development may in fact be a delayed immune response. This hypothesis is supported by the finding that lymphocyte cultures obtained from chronically exposed workers underwent a high degree of blast formation when challenged with beryllium sulfate (137). The authors suggest that this test may serve as a screen for detecting hypersensitive individuals. 

A variety of techniques have been employed to assess the immune response to beryllium. Ho vever, the ease, sensitivity, and specificity have made the lymphocyte proliferation assay using H-thymidine the standard technique (Rossman et al. 1988, Mroz et al. 1991). In the past, this technique has been referred to as the lymphocyte transformation test (LTT), but transformation is an older term that is no longer applicable. The cells respond by proliferating (a normal process) and are not transformed, which today implies a malignant process. Hence, the test is currently known as the lymphocyte proliferation test (LPT). 

The reactivity of either blood or bronchoal-veolar lymphocytes to beryllium can be determined using the LPT. To test peripheral blood, a sample of heparinized blood should be centrifuged over Ficoll-Hypaque to obtain blood mononuclear cells (-70% lymphocytes and 30% monocytes). Cells obtained by bronchoalveolar lavage can be used after washing (Rossman et al. 1988). While the major published studies have utilized bronchoalveolar cells in this manner, occasionally other techniques are employed to enhance the proliferative response of... 

Meoz NM, Kreiss K, Lezotte KD, Campbell PA. and Newman LS (1991) Reexamination of the blood lymphocyte transformation test in the diagnosis of chronic beryllium disease. J Allergy Clin Immunol 88 54-60. 

Epstein PE, Preuss O. P, Markham TN and Daniele RP (1988) Proliferative response ofbron-choalveolar lymphocytes to beryllium. A test for chronic beryllium disease. Ann Intern Med 108 687-693. 

Further studies on the cell-mediated immune response have determined that only a subset of lymphocytes, those known as helper T cells (CD4+ T cells), respond to beryllium by a proliferative response [23]. This proliferative response can be blocked with antibodies to class II molecules. 

Despite all the problems listed above concerning the detection of a cell-mediated immune response to beryllium, the lymphocyte proliferative response to beryllium by bronchoalveolar cells is part of the currently accepted gold standard diagnosis for chronic beryllium disease [40]. 

In the guinea pig, intratracheal instillation of 75 mg beryllium metal after 3 months induced focal lymphocytic and large mononuclear cell reaction immediately about visible deposits of the substance (VORWALD 1950). 

In the guinea pig, zinc beryllium manganese silicate inhalation (8 h/d) for 40 months induced mild lymphocytic and large mononuclear cell reaction indicative of slight irritation about dust particles (Vorwald 1950). 

Exposure to elevated concentrations of beryllium, usually in the 25 pg/m range or greater, (120) can result in inflammation of the upper and lower respiratory tract and airways, tracheitis, bronchiolitis, pulmonary edema, and a lymphocyte-predominant chemical pneumonitis (12,121-123). Although significantly less common than CBD, acute beryllium disease stiU occurs globally. In 2004, nine cases were reported from a South Korean liquid metal factory where measured beryllium exposures ranged from 3.13 to 112.3 pg/m (12). The manifestations... 

WilUams WR, Jones-WiUiams W. Comparison of lymphocyte transformation and macrophage migration inhibition tests in the detection of beryllium hypersensitivity. J Clin Pathol 1982 35(6) 684-687. 

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