Utility of quantitative T-cell responses versus unstimulated interferon-{gamma} for the diagnosis of pleural tuberculosis

• Published in: The European respiratory journal Vol. 34; no. 5; pp. 1118 - 1126
• Main Authors: Dheda, K, van Zyl-Smit, R. N, Sechi, L. A, Badri, M, Meldau, R, Meldau, S, Symons, G, Semple, P. L, Maredza, A, Dawson, R, Wainwright, H, Whitelaw, A, Vallie, Y, Raubenheimer, P, Bateman, E. D, Zumla, A
• Format: Journal Article
• Language: English
• Published: England Eur Respiratory Soc 01.11.2009
• Subjects: Adult; Aged; Chemistry, Clinical - methods; Cohort Studies; Female; Humans; Interferon-gamma - pharmacology; Leukocytes, Mononuclear - immunology; Male; Middle Aged; Pulmonary Medicine - methods; Pulmonary Medicine - standards; Reproducibility of Results; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Treatment Outcome; Tuberculosis, Pleural - blood; Tuberculosis, Pleural - diagnosis; Tuberculosis, Pleural - immunology
• ISSN: 0903-1936; 1399-3003
• DOI: 10.1183/09031936.00005309

The clinical utility of antigen-specific interferon (IFN)-gamma release assays (IGRAs) using pleural mononuclear cells, for the diagnosis of tuberculosis (TB), requires clarification. We compared the diagnostic utility of unstimulated pleural IFN-gamma levels with several pleural antigen-specific T-cell IGRAs (early secretory antigenic target-6 and culture filtrate protein-10 (T-SPOT.(R)TB, QuantiFERON(R)-TB Gold In-tube), purified protein derivative (PPD) and heparin-binding haemagglutinin (HBHA)) in 78 South African TB suspects. Test results were compared against a clinical score and a reference standard. Out of 74 evaluable subjects 48, seven and 19 had definite, probable and no TB, respectively. 11 (15%) out of 74 pleural samples (nine (19%) out of 48 of the definite TB cases) had total cell counts that were inadequate for T-cell processing. In the remaining 63 samples, the sensitivity, specificity, positive predictive value and negative predictive value of different diagnostic methods were as follows. Maximal bioclinical score: 54, 89, 92 and 43%, respectively; T-SPOT.(R)TB: 86, 60, 84 and 64%, respectively; QuantiFERON(R)-TB Gold In-tube: 57, 80, 87 and 44%, respectively; HBHA-specific IGRA: 59, 31, 64 and 27%, respectively; PPD-specific IGRA: 81, 40, 76 and 46%, respectively; and pleural fluid unstimulated IFN-gamma: 97, 100, 100 and 94%, respectively. Unstimulated IFN-gamma was the most accurate test for distinguishing TB from non-TB effusions in a high-burden setting. The antigen-specific T-cell IGRAs were limited by suboptimal accuracy and the inability to isolate sufficient mononuclear cells to perform the assay.