title: Utility of quantitative T-cell responses versus unstimulated interferon-{gamma} for the diagnosis of pleural tuberculosis.
abstract: 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.
authors.affiliation: Lung Infection and Immunity Unit, Division of Pulmonology, Dept of Medicine, University of Cape Town, J flr, Old Main Bldg, Groote Schuur Hospital, Observatory, Cape Town 7925, South Africa. keertan.dheda@uct.ac.za
authors.forename: K
authors.initials: K
authors.lastname: Dheda
authors.forename: R N
authors.initials: RN
authors.lastname: van Zyl-Smit
authors.forename: L A
authors.initials: LA
authors.lastname: Sechi
authors.forename: M
authors.initials: M
authors.lastname: Badri
authors.forename: R
authors.initials: R
authors.lastname: Meldau
authors.forename: S
authors.initials: S
authors.lastname: Meldau
authors.forename: G
authors.initials: G
authors.lastname: Symons
authors.forename: P L
authors.initials: PL
authors.lastname: Semple
authors.forename: A
authors.initials: A
authors.lastname: Maredza
authors.forename: R
authors.initials: R
authors.lastname: Dawson
authors.forename: H
authors.initials: H
authors.lastname: Wainwright
authors.forename: A
authors.initials: A
authors.lastname: Whitelaw
authors.forename: Y
authors.initials: Y
authors.lastname: Vallie
authors.forename: P
authors.initials: P
authors.lastname: Raubenheimer
authors.forename: E D
authors.initials: ED
authors.lastname: Bateman
authors.forename: A
authors.initials: A
authors.lastname: Zumla
mesh_terms: D000328:Adult; D000368:Aged; D002624:Chemistry, Clinical / Q000379:methods; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015272:Pulmonary Medicine / Q000379:methods / Q000592:standards; D015203:Reproducibility of Results; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D016896:Treatment Outcome; D014396:Tuberculosis, Pleural / Q000097:blood* / Q000175:diagnosis* / Q000276:immunology*
chemical_list: D007371:Interferon-gamma