Key result
Pleural fluid CARD17, GBP2, and C1QB gene expression discriminates pleural TB with up to ~91% accuracy.
Why the study?
Data using transcriptional signatures for extrapulmonary tuberculosis, specifically pleural tuberculosis, are scarce and heterogeneous, making diagnosis and management challenging.
Does a transcriptional signature in pleural fluid accurately discriminate pleural tuberculosis from other causes of exudative pleural effusion?
Observational (n=69)
No
Does a transcriptional signature in pleural fluid accurately discriminate pleural tuberculosis from other causes of exudative pleural effusion?
The expression of CARD17, GBP2, and C1QB genes in pleural fluid provides a highly accurate transcriptional signature for diagnosing pleural tuberculosis.
May support pleural fluid gene signatures for TB diagnosis; leaves open prospective validation before clinical use.
Introduction Pleural tuberculosis (PlTB), the most common site of extrapulmonary TB, is characterized by a paucibacillary nature and a compartmentalized inflammatory response in the pleural cavity, both of which make diagnosis and management extremely challenging. Although transcriptional signatures for pulmonary TB have already been described, data obtained by using this approach for extrapulmonary tuberculosis and, specifically, for pleural tuberculosis are scarce and heterogeneous. In the present study, a set of candidate genes previously described in pulmonary TB was evaluated to identify and validate a transcriptional signature in clinical samples from a Brazilian cohort of PlTB patients and those with other exudative causes of pleural effusion. Methods As a first step, target genes were selected by a random forest algorithm with recursive feature elimination (RFE) from public microarray datasets. Then, peripheral blood (PB) and pleural fluid (PF) samples from recruited patients presenting exudative pleural effusion were collected during the thoracentesis procedure. Transcriptional analysis of the selected top 10 genes was performed by quantitative RT-PCR (RT-qPCR). Results Reanalysis of the public datasets identified a set of candidate genes ( CARD17, BHLHE40, FCGR1A, BATF2, STAT1, BTN3A1, ANKRD22, C1QB, GBP2 , and SEPTIN4 ) that demonstrated a global accuracy of 89.5% in discriminating pulmonary TB cases from other respiratory diseases. Our validation cohort consisted of PlTB ( n = 35) patients and non-TB ( n = 34) ones. The gene expressions of CARD17 , GBP2 , and C1QB in PF at diagnosis were significantly different between the two (PlTB and non-TB) groups ( p < 0.0001). It was observed that the gene expressions of CARD17 and GBP2 were higher in PlTB PF than in non-TB patients. C1QB showed the opposite behavior, being higher in the non-TB PF. After anti-TB therapy, however, GBP2 gene expression was significantly reduced in PlTB patients ( p < 0.001). Finally, the accuracy of the three above-cited highlighted genes in the PF was analyzed, showing AUCs of 91%, 90%, and 85%, respectively. GBP2 was above 80% (sensitivity = 0.89/specificity = 0.81), and CARD17 showed significant specificity (Se = 0.69/Sp = 0.95) in its capacity to discriminate the groups. Conclusion CARD17 , GBP2 , and C1QB showed promise in discriminating PlTB from other causes of exudative pleural effusion by providing accurate diagnoses, thus accelerating the initiation of anti-TB therapy.
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Corrêa et al. (2024) conducted an observational in Pleural effusion (Pleural tuberculosis vs. non-tuberculosis) (n=69). CARD17, GBP2, and C1QB gene expression vs. Non-tuberculosis pleural effusion was evaluated on Discrimination of pleural tuberculosis from non-tuberculosis using CARD17 gene expression in pleural fluid (AUC 0.91, 95% CI 0.83-0.99, p=<0.0001). CARD17, GBP2, and C1QB gene expression in pleural fluid accurately discriminated pleural tuberculosis from other causes of exudative pleural effusion, with AUCs of 91%, 90%, and 85%, respectively.
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