Diagnostic value of ex vivo pleural fluid interferon-gamma versus adapted whole-blood quantiferon-TB gold in tube assays in tuberculous pleural effusion

Abstract

BACKGROUND:Noninvasive diagnosis of pleural tuberculosis (TB) remains a challenge due to the paucibacillary nature of the disease. As Mycobacterium tuberculosis (MTB)-specific T cells are recruited into pleural space in TB effusion; their indirect detection may provide useful clinical information.OBJECTIVES:Evaluation of pleural fluid interferon (INF)-γ levels vs Quantiferon–TB Gold In tube assay (QFT- IT) in blood and its adapted variants, using pleural fluid or isolated pleural fluid cells in the diagnosis of pleural TB.METHODS:Thirty-eight patients with pleural effusion of unknown etiology presented at Assiut University Hospital, Egypt, were recruited. Blood and pleural fluid were collected at presentation for INF-γ assays. Ex vivo pleural fluid INF-γ levels, QFT-IT in blood and its adapted variants were compared with final diagnosis as confirmed by other tools including blind and/or thoracoscopic pleural biopsy.RESULTS:The final clinical diagnosis was TB in 20 (53%), malignancy in 10 (26%), and effusion due to other causes in eight patients (21%). Ex vivo pleural fluid INF-γ levels accurately identified TB in all patients and were superior to the QFT-IT assays using blood or pleural fluid (70 and 78% sensitivity, with 60 and 83% specificity, respectively). QFT-IT assay applied to isolated pleural fluid cells had 100% sensitivity and 72% specificity. The optimal cut-off obtained with ROC analysis was 0.73 for TB Gold assay in blood assay, 0.82 IU/ml for the cultured pleural fluid assay, and 0.94 for isolated pleural cells assay.CONCLUSION:The ex vivo pleural fluid INF-γ level is an accurate marker for the diagnosis of pleural TB. QFT- IT assay in peripheral blood or its adapted versions of the assay using pleural fluid and/or washed pleural fluid cells had no diagnostic advantage over pleural fluid INF-γ in the diagnosis of pleural TB.

Interferon Gamma Release Assays for Diagnosis of Pleural Tuberculosis: a Systematic Review and Meta-Analysis

“…All studies except one provided details on the reference standards used to diagnose TPE (30). In five studies, every TPE patient had definite TB (17,21,22,29,36). In five other studies, Ͼ75% TPE patients had a similar definite diagnosis (Table 1) (19,24,27,31,35).…”

“…Manufacturer-specified thresholds were used to categorize results in all but five studies. These five studies either used a modified threshold or derived one from receiver operating characteristic curves and hence did not report indeterminate results (20,22,28,34,36). Two studies excluded patients with indeterminate results prior to analysis (18,27).…”

Accuracy of the interferon-gamma release assay for the diagnosis of tuberculous pleurisy: an updated meta-analysis

“…1 . In the end, 15 publications of IGRA to diagnose patients with TP were eligible for inclusion ( Wilkinson et al, 2005 ; Ariga et al, 2007 ; Losi et al, 2007 ; Baba et al, 2008 ; Chegou et al, 2008 ; Dheda et al, 2009 ; Lee et al, 2009 ; Keng et al, 2013 ; Ates et al, 2011 ; Eldin et al, 2012 ; Kang et al, 2012 ; Liu et al, 2013 ; Liao et al, 2014 ; Chung et al, 2011 ; Gao et al, 2012 ). In the studies by Dheda et al (2009) and Kang et al (2012) , IGRA was performed in two formats: as an enzyme-linked immunosorbent spot (ELISPOT) assay, and as an enzyme-linked immunosorbent assay (ELISA).…”

Diagnostic performance of interferon-Gamma assay for tuberculosis in immunocompromised patients

“…who investigated the utility of interferon (INF)-γ level and Quantiferon-TB Gold In tube (QFT-GIT) assay for the diagnosis of pleural tuberculosis (TB). [1] They concluded the ex vivo pleural fluid INF-γ levels is an accurate diagnostic tool for pleural TB. [1]…”

“…[1] They concluded the ex vivo pleural fluid INF-γ levels is an accurate diagnostic tool for pleural TB. [1]…”