Infection and Drug Resistance (May 2019)

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

  • Shi W,
  • Wu J,
  • Tan Q,
  • Hu CM,
  • Zhang X,
  • Pan HQ,
  • Yang Z,
  • He MY,
  • Yu M,
  • Zhang B,
  • Xie WP,
  • Wang H

Journal volume & issue
Vol. Volume 12
pp. 1265 – 1276

Abstract

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Wen Shi,1 Juan Wu,1 Qi Tan,1 Chun-Mei Hu,2 Xia Zhang,2 Hong-Qiu Pan,3 Zhen Yang,4 Meng-Yu He,1 Min Yu,1 Bo Zhang,5 Wei-Ping Xie,1 Hong Wang11Department of Respiratory and Critical Care Medicine, Jiangsu Province Hospital. The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 2Department of Tuberculosis, The Second Hospital of Nanjing, Nanjing, Jiangsu Province, People’s Republic of China; 3Department of Tuberculosis, The Third Hospital of Zhenjiang City, Zhenjiang, Jiangsu Province, People’s Republic of China; 4Department of Respiratory Medicine, Jiangbei Hospital, Nanjing, Jiangsu Province, People’s Republic of China; 5Department of Population and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA, USAPurpose: 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.Keywords: IDO, MDR-TB, LC-MS/MS, cavitary lung lesion

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