Utility of quantitative T-cell responsesversusunstimulated interferon-γ for the diagnosis of pleural tuberculosis

Abstract

The clinical utility of antigen-specific interferon (IFN)-c release assays (IGRAs) using pleural mononuclear cells, for the diagnosis of tuberculosis (TB), requires clarification.We compared the diagnostic utility of unstimulated pleural IFN-c levels with several pleural antigen-specific T-cell IGRAs (early secretory antigenic target-6 and culture filtrate protein-10 (T-SPOT.1TB, QuantiFERON1-TB Gold In-tube), purified protein derivative (PPD) and heparinbinding 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.1TB: 86, 60, 84 and 64%, respectively; QuantiFERON1-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-c: 97, 100, 100 and 94%, respectively. Unstimulated IFN-c 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.

Cerebrospinal T-Cell Responses Aid in the Diagnosis of Tuberculous Meningitis in a Human Immunodeficiency Virus– and Tuberculosis-Endemic Population

“…This is similar to findings when using alveolar lavage cells in high- (22) and low-burden settings (23). In contrast, the specificity of the assay is poor in the pleural compartment (25) where patients with non-TB diagnoses (e.g., malignancy may have a high frequency of antigen-specific T cells). This may reflect the cellular translocation dynamics of different compartments, and in patients with LTBI there may be a compartment-specific leak of reactive T cells down a chemokine gradient (42).…”

“…An alternative approach is to quantify the frequency of antigen-specific effector cells at the site of disease rather than in whole blood. This approach has recently been shown to be highly accurate when using bronchial alveolar lavage lymphocytes to diagnose pulmonary TB (22)(23)(24) but not when using site-specific lymphocytes to diagnose pleural TB (25). Case reports and small series suggest that this approach may also be useful for the diagnosis of TBM (26)(27)(28)(29).…”

“…A count of 20 or higher SFCs per million cells in the ESAT-6 or CFP-10 wells was deemed a positive result (see online supplement for further details). Given the use of different cut points in specific body compartments (22,25) when compared with peripheral blood and that none has been defined for CSF, which has unique physiologic and anatomic characteristics, we derived new cut-offs using receiver operating characteristic (ROC) curves analysis. The manufacturer's cut-off and cut-offs generated from the study were used for reporting results.…”

Diagnosis of tuberculosis infection using interferon-γ-based assays

“…79 Commercial IFN-γ tests, T-SPOT.TB and QFT-IT in pleural fluid were compared to unstimulated IFN-γ for the diagnosis of pleural TB in 74 patients. 80 In 11 (15%) cases, the cell counts were not large enough to perform the tests. In the 63 remaining patients, sensitivity, specificity, positive predictive value and negative predictive value were: for T-SPOT.TB, 86, 60, 84 and 64% respectively; for QFT-IT, 57, 80, 87 and 44% respectively, and for unstimulated IFN-γ, 97, 100, 100 and 94% respectively.…”

Interferon-γ release assays for diagnosis of active pleural tuberculosis: a developing world perspective

“…Although the method is very sensitive, it was, using strict criteria for active infection, deemed not specific enough for the correct diagnosis of active pleural TB to be routinely recommended. Measurement of unstimulated interferon-c in pleural effusions could be more accurate to distinguish TB from non-TB aetiologies in regions of high TB incidence [12].…”