Schiff, Hannah, Walker, Naomi F., Ugarte-Gil, Cesar, Tebruegge, Marc, Garbis, Spiros D., Manousopoulou, Antigoni, Mansour, Salah, Wong, Pak Ho, Rockett, Gabrielle, Piazza, Paolo, Niranjan, Mahesan, Vallejo, Andres F., Woelk, Christopher H., Wilkinson, Robert J., Tezera, Liku B., Garay Baquero, Diana and Elkington, Paul (2024) Integrated plasma proteomics identifies tuberculosis-specific diagnostic biomarkers. JCI Insight. (doi:10.1172/jci.insight.173273).
Abstract
Background: novel biomarkers to identify infectious patients transmitting Mycobacterium tuberculosis are urgently needed to control the global tuberculosis (TB) pandemic. We hypothesized that proteins released into the plasma in active pulmonary TB are clinically useful biomarkers to distinguish TB cases from healthy individuals and patients with other respiratory infections.
Methods: we applied a highly sensitive non-depletion tandem mass spectrometry discovery approach to investigate plasma protein expression in pulmonary TB cases compared to healthy controls in South African and Peruvian cohorts. Bioinformatic analysis using linear modeling and network correlation analyses identified 118 differentially expressed proteins, significant through
3 complementary analytical pipelines. Candidate biomarkers were subsequently analyzed in 2 validation cohorts of differing ethnicity using antibody-based proximity extension assays.
Results: TB-specific host biomarkers were confirmed. A 6-protein diagnostic panel, comprising FETUB, FCGR3B, LRG1, SELL, CD14, and ADA2, differentiated patients with pulmonary TB from healthy controls and patients with other respiratory infections with high sensitivity and specificity in both cohorts.
Conclusion: this biomarker panel exceeds the World Health Organization Target Product Profile specificity criteria for a triage test for TB. The new biomarkers have potential for further development as near-patient TB screening assays, thereby helping to close the case-detection gap that fuels the global pandemic.
More information
Identifiers
Catalogue record
Export record
Altmetrics
Contributors
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.