Metabolomic Profiling of Plasma from Patients with Tuberculosis by Use of Untargeted Mass Spectrometry Reveals Novel Biomarkers for Diagnosis

摘要: Although tuberculosis (TB) is a reemerging disease that affects people in developing countries and immunocompromised populations developed countries, the current diagnostic methods are far from optimal. Metabolomics increasingly being used for studies on infectious diseases. We performed metabolome profiling of plasma samples to identify potential biomarkers diagnosing TB. compared profiles TB patients (n = 46) with those community-acquired pneumonia (CAP) 30) controls without active infection using ultrahigh-performance liquid chromatography-electrospray ionization-quadrupole time flight mass spectrometry (UHPLC-ESI-QTOFMS). Using multivariate univariate analyses, four metabolites, 12R-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid [12(R)-HETE], ceramide (d18:1/16:0), cholesterol sulfate, 4α-formyl-4β-methyl-5α-cholesta-8-en-3β-ol, were identified found have significantly higher levels than CAP controls. In comparison controls, metabolites demonstrated area under receiver operating characteristic curve (AUC) values 0.914, 0.912, 0.905, 0.856, sensitivities 84.8%, 87.0%, 89.1%, specificities 90.0%, 86.7%, 80.0%, fold changes 4.19, 26.15, 6.09, 1.83, respectively. patients, AUC 0.793, 0.717, 0.802, 0.894, 71.7%, 80.4%, 63.3%, 66.7%, 70.0%, 83.3%, 4.69, 3.82, 3.75, 2.16, 4α-Formyl-4β-methyl-5α-cholesta-8-en-3β-ol combined 12(R)-HETE or sulfate offered ≥70% sensitivity ≥90% specificity differentiating patients. These novel biomarkers, especially alone combination, potentially useful rapid noninvasive diagnosis The present findings may offer insights into pathogenesis host response