Beryllium-stimulated neopterin as a diagnostic adjunct in chronic beryllium disease.
BACKGROUND
The diagnosis of chronic beryllium disease (CBD) relies on the beryllium lymphocyte proliferation test (BeLPT) to demonstrate a Be specific immune response. This test has improved early diagnosis, but cannot discriminate beryllium sensitization (BeS) from CBD. We previously found high neopterin levels in CBD patients' serum and questioned whether Be-stimulated neopterin production by peripheral blood cells in vitro might be useful in the diagnosis of CBD.


METHODS
CBD, BeS, Be exposed workers without disease (Be-exp) normal controls and sarcoidosis subjects were enrolled. Peripheral blood mononuclear cells (PBMN) were cultured in the presence and absence of beryllium sulfate. Neopterin levels were determined from cell supernatants by enzyme linked immunosorbent assay (ELISA). Clinical evaluation of CBD subjects included chest radiography, pulmonary function testing, exercise testing, and the BeLPT.


RESULTS
CBD patients produced higher levels of neopterin in both unstimulated and Be-stimulated conditions compared to all other subjects (P < 0.0001). Unstimulated neopterin mononuclear cell levels overlapped among groups, however, Be-stimulated neopterin levels in CBD showed little overlap. Using a neopterin concentration of 2.5 ng/ml as a cutoff, Be-stimulated neopterin had a sensitivity of 80% and specificity of 100% for CBD and was able to differentiate CBD from BeS. Be-stimulated neopterin was inversely related to measures of pulmonary function, exercise capacity, and gas exchange.


CONCLUSIONS
Neopterin may be a useful diagnostic adjunct in the non-invasive assessment of CBD, differentiating CBD from BeS. Further studies will be required to determine how it performs in workplace screening.
Maier
Lisa A
LA
Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado, USA. maierL@njc.org
Kittle
Lori A
LA
Mroz
Margaret M
MM
Newman
Lee S
LS
D000328:Adult; D001607:Berylliosis / Q000175:diagnosis*; D001608:Beryllium / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002478:Cells, Cultured; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005080:Exercise Test; D005260:Female; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood*; D016273:Occupational Exposure / Q000032:analysis*; D011859:Radiography; D012129:Respiratory Function Tests; D017565:Sarcoidosis, Pulmonary / Q000175:diagnosis; D012680:Sensitivity and Specificity
D015415:Biomarkers; D019798:Neopterin; D001608:Beryllium