Use of T-SPOT.TB for the diagnosis of unconventional pleural tuberculosis is superior to ADA in high prevalence areas: A prospective analysis of 601 cases

Abstract BACKGROUND: Tuberculous pleural effusion (TPE) is the most common extrapulmonary manifestation and may have lasting effect on lung function. however conventional diagnostic tests for TPE register multiple limitations. OBJECTIVES: To investigate diagnostic efficacy of the interferon gamma release assay (IGRA: T-SPOT.TB) in TPE patients of different characteristics. METHODS: We performed a prospective, single-centre study including all suspected pleural effusion patients consecutively from June 2015 to October 2018. By using receiver operating characteristic (ROC) curves, technical cut-offs for all enrolled participants were determined, and the utility of T-SPOT on pleural fluid (PF) was analysed. We obtained the independent risk factors using logistic regression analysis for TPE and evaluated the performance of the T-SPOT assay stratified by risk factors in comparison to ADA. RESULTS: A total of 601 individuals was consecutively recruited. The maximum spot-forming cells (SFCs) of early secretory antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) in the PF T-SPOT assay had the best diagnostic efficiency in our study, which was equal to ADA (0.885 vs 0.887, P=0.957) and superior to PB, with a sensitivity of 83.0% and a specificity of 83.1% (The cut-off value was 466 SFCs/10 6 mononuclear cells). Among the TPE patients with low ADA (<40 IU/L), the sensitivity and specificity of PF T-SPOT were still 87.9% and 90.5%, respectively. The utility of ADA was negatively related to increasing age, but the PF T-SPOT test had a steady performance at all ages. Age (<45 yrs; odds ratio (OR) = 5.61, 95% confidence interval (CI) 3.59-8.78; P <0.001), gender (male; OR = 2.68, 95% CI 1.75-2.88; P <0.001) and body mass index (BMI) (<22; OR = 1.93, 95% CI 1.30-2.88; P =0.001) were independently associated with the risk of TB by multivariate logistic regression analysis. Notably, when stratified by risk factor, the sensitivity of PF T-SPOT was superior to the sensitivity (76.5% vs. 23.5%, P =0.016) for ADA and had noninferior specificity (84.4% vs. 96.9%, P =0.370). CONCLUSIONS: In conclusion, the overall potency of the PF T-SPOT assay is equal to that of ADA for diagnosing TPE. In addition, the PF T-SPOT assay can effectively discriminate TPE patients whose ADA is lower than 40 IU/L and is extremely superior to ADA in unconventional TPE patients (age≥45 yrs, female or BMI≥22). The PF T-SPOT assay is an excellent choice to supplement ADA to diagnose TPE.