Immunologic and genetic testing in beryllium disease

The beryllium lymphocyte proliferation test (BeLPT) is an immunological assay used to identify sensitivity to beryllium and assist in the diagnosis of chronic beryllium disease (CBD). The test is widely used for surveillance and screening in worker populations. As with all clinical screening tests, the positive predictive value (PPV) is highly influenced by the pre-test probability of disease. The PPV for CBD ranges from 9 % (former USDOE construction workers) to 100% (beryllium oxide ceramics workers). The PPV for CBD is also increased with increasing time between initial (negative) screening and subsequent testing, reflecting the importance of variable latency periods in the disease course. For example screening of former DOE production workers at Rocky Flats (1996) produced a PPV of 45% compared with 24% for current workers in the same program.

Genetic polymorphisms in the population influence susceptibility to beryllium exposure. For example, Human Leukocyte Antigen gene variant, HLA-DP beta 1*0201, contains a substitution of glutamate for lysine at position 69 that appears to have high sensitivity (approximately 94%) but low specificity (approximately 70%) with respect to CBD among workers exposed to beryllium. Testing workers for such a polymorphism might be considered (1) as a required job placement screen, (2) as a risk-based guide to the frequency of future lymphocyte proliferation testing, or (3) as a voluntary job placement screen. This presentation will provide the background information on these two tests to prepare for the point-counterpoint discussion by subsequent presenters.