Mass Spectrometric Identification of Urinary Biomarkers of Pulmonary Tuberculosis

Background: Tuberculosis (TB) is the leading infectious cause of death worldwide. A major barrier to control of the pandemic is a lack of clinical biomarkers with the ability to distinguish active TB from healthy and sick controls and potential for development into point-of-care diagnostics. Methods: We conducted a prospective case control study to identify candidate urine-based diagnostic biomarkers of active pulmonary TB (discovery cohori) and obiained a separate blinded "validation" cohort of confirmed cases of active pulmonary TB and controls with non-Luberculous pulmonary disease for validation. Clean-caLch urine samples were collected and analyzed using high performance liquid chromaLography-coupled Lime-of-flight mass spectrometry. Results: We discovered ten molecules from the discovery cohort with receiver-operator characteristic (ROC) area-under-the-curve (AUC) values >85%. These 10 molecules also significantly decreased after 60 days of treatment in a subset of 20 participants followed over time. Of these, a specific combination of diacetylspermine, neopterin, sialic acid, and N-acetylhexosamine exhibited ROC AUCs >80% in a blinded validation cohort of participants with active TB and non-tuberculous pulmonary disease. Conclusion: Urinary levels of diacetylspermine, neoptelin, sialic acid, and N-acetylhexosa mine distinguished patients with tuberculosis from healthy controls and patients with non-tuberculous pulmonary diseases, providing a potential noninvasive biosignature of active TB. (C) 2018 The Author(s). Published by Elsevier B.V.