Integrated plasma proteomics identifies tuberculosis-specific diagnostic biomarkers

Schiff, Hannah F., Walker, Naomi ORCID: https://orcid.org/0000-0002-3345-7694, Ugarte-Gil, Cesar, Tebruegge, Marc, Manousopoulou, Antigoni, Garbis, Spiros D., 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, Vol 9, Issue 8, e173273.

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Abstract

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. 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 modelling and network correlation analyses identified 118 differentially expressed proteins, significant through three complementary analytical pipelines. Candidate biomarkers were subsequently analysed in two validation cohorts of differing ethnicity using antibody-based proximity extension assays. TB-specific host biomarkers were confirmed. A six-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. This biomarker panel exceeds the World Health Organisation 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.

Item Type:	Article
Subjects:	QU Biochemistry > Genetics > QU 460 Genomics. Proteomics WF Respiratory System > Tuberculosis > WF 200 Tuberculosis (General) WF Respiratory System > Tuberculosis > WF 220 Diagnosis. Prognosis
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1172/jci.insight.173273
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	10 Apr 2024 12:09
Last Modified:	16 Sep 2024 09:55
URI:	https://archive.lstmed.ac.uk/id/eprint/24303

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