Mass Spectrometric Identification of Urinary Biomarkers of Pulmonary Tuberculosis

EBioMedicine
Flonza IsaKyu Y Rhee

Abstract

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. We conducted a prospective case control study to identify candidate urine-based diagnostic biomarkers of active pulmonary TB (discovery cohort) and obtained a separate blinded "validation" cohort of confirmed cases of active pulmonary TB and controls with non-tuberculous pulmonary disease for validation. Clean-catch urine samples were collected and analyzed using high performance liquid chromatography-coupled time-of-flight mass spectrometry. 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. Urinary levels of diacetylspe...Continue Reading

Citations

Apr 1, 2019·The Journal of Infectious Diseases·Paul ElkingtonLarry S Schlesinger
Oct 24, 2020·Scientific Reports·Wei LiuDong-Lai Ma
Apr 23, 2019·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Carlos A M SilvaMary Ann De Groote
Jun 15, 2021·Molecular Omics·Vivian TountaGerald Larrouy-Maumus

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Methods Mentioned

BETA
urine sample collection

Software Mentioned

Agilent Technologies Qualitative analysis
R
STATA
GeneXpert
Agilent Molecular Structure Correlator
RRmix

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