Plasma indoleamine 2,3-dioxygenase activity as a potential biomarker for early diagnosis of multidrug-resistant tuberculosis in tuberculosis patients

Abstract

Purpose: Multidrug-resistant tuberculosis (MDR-TB) remains a challenge of global TB control, with difficulty in early detection of drug-sensitive tuberculosis (DS-TB). We investigate the diagnostic significance of IDO as a potential biomarker to discriminate MDR patients among the TB patients. Patients and methods: Plasma indoleamine 2,3-dioxygenase (IDO) was measured by the ratio of kynurenine (Kyn) to tryptophan (Trp) concentrations, using high performance liquid chromatography-mass spectrometry (LC-MS/MS). Chest computed tomography (CT) imaging signs from TB patients were collected and analyzed in 18 DS-TB patients, 16 MDR-TB patients, 6 lung cancer (LC) patients, and 11 healthy individuals. Lung imaging signs from TB patients were collected and analyzed. Results: We found that plasma IDO activity was significantly higher in the MDR-TB patients than in the DS-TB patients (p=0.012) and in the LC patients (p=0.003). We evaluated the diagnostic significance of plasma IDO activity in discriminating the MDR-TB group from the DS-TB group using a receiver operating characteristic (ROC) curve. With a cutoff level of 46.58 uM/mM, the diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for IDO activity were 87.50%, 72.22%, 73.68%, and 86.67%, respectively. Plasma IDO activity was higher in cavity cases than in non-cavity cases (p=0.042), proving a positive correlation between lung cavity number and cavity size (p<0.05, separately) among all the TB patients studied. Conclusion: Our findings confirmed that plasma IDO activity might have an auxiliary diagnosis value for early discrimination of MDR-TB patients from DS-TB patients. Among the TB patients with cavitary lung lesions, higher plasma IDO activity can indicate a higher risk of MDR-TB.