Diagnostic Accuracy of Pleural Fluid Interferon-Gamma for Tuberculous Pleural Effusion: A Prospective Cross-Sectional Study

Abstract

Tuberculous pleural effusion (TPE) remains difficult to diagnose because pleural disease is often paucibacillary, and conventional microbiological tests have limited sensitivity. This prospective cross-sectional diagnostic accuracy study evaluated pleural fluid interferon-gamma (IFN-γ) as a host-response biomarker for TPE. Consecutive adults undergoing clinically indicated thoracentesis at referral hospitals in Makassar, Indonesia, were enrolled, and residual pleural fluid was analyzed using a quantitative sandwich ELISA. Eighty-eight participants were included: 28 with TPE, 30 with parapneumonic pleural effusion (PPE), and 30 with malignant pleural effusion (MPE). Median IFN-γ concentrations were significantly higher in TPE than in non-TPE [803.53 (566.75–1058.06) vs 19.14 (5.50–80.75) pg/mL; p<0.001] and differed significantly across TPE, PPE, and MPE (p<0.001), with higher levels in TPE than in either comparator. Receiver operating characteristic analysis yielded an area under the curve of 0.992 (95% CI, 0.979–1.000). At the study-derived threshold of ≥346.52 pg/mL, sensitivity was 100.0%, specificity 96.7%, positive predictive value 93.3%, negative predictive value 100.0%, and overall accuracy 97.7%. Pleural fluid IFN-γ showed excellent discrimination for TPE and may be useful as an adjunctive diagnostic biomarker; however, the proposed threshold requires external validation before routine clinical use.