Diagnostic Utility of Pleural Fluid T-SPOT and Interferon-gamma for Tuberculous Pleurisy: A Two-Center Prospective Cohort Study in China

Abstract Background Early and accurate diagnosis of tuberculous pleurisy (TP) remains challenging. The aim of the present study is to evaluate the performance of pleural fluid (PF) T-SPOT and interferon-gamma (IFN-γ) for TP diagnosis in high tuberculosis (TB)-burden settings. Methods In total, 214 and 217 subjects suspected of TP were prospectively enrolled in Wuhan (training) cohort and Changchun (validation) cohort, respectively. All patients were examined with PF T-SPOT, IFN-γ, and other traditional tests simultaneously. Results The receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC), sensitivity, and specificity of TB-specific antigen (TBAg) spot-forming cells (SFC) (the larger of early secreted antigenic target 6 and culture filtrate protein 10 SFC in PF T-SPOT assay) for TP diagnosis were 0.972, 92.86%, and 92.16% respectively, with a cut-off value of 35 in Wuhan cohort. Meanwhile, when a threshold value of 95 ng/mL was set, the AUC, sensitivity, and specificity of IFN-γ to diagnose TP were 0.951, 86.61%, and 90.20% respectively. Moreover, the diagnostic model based on combination of TBAg SFC and IFN-γ showed an AUC of 0.983 for differentiating TP from non-TP, with 95.54% sensitivity and 95.10% specificity when a cutoff value of 0.32 was used in Wuhan cohort. Excellent diagnostic accuracy was also observed in Changchun cohort. When applying the cutoff value obtained from Wuhan cohort, the AUC, sensitivity, and specificity of diagnostic model were 0.995, 95.08%, and 97.89% respectively. Conclusions The performance of PF T-SPOT was comparable to IFN-γ in diagnosing TP. However, using the diagnostic model established by combination of these two assays can achieve a more accurate diagnosis of TP.