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Integrated plasma proteomics identifies tuberculosis-specific diagnostic biomarkers
Hannah F Schiff1,2, Naomi F Walker3, Cesar Ugarte-Gil4,5
1NIHR Biomedical Research Centre, School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
JCI Insight
|March 21, 2024
Summary
New protein biomarkers in the blood can accurately detect active pulmonary tuberculosis (TB) and distinguish it from other respiratory illnesses. This discovery offers a promising tool for near-patient screening to combat the global TB pandemic.
Area of Science:
- Biochemistry and Molecular Biology
- Infectious Diseases
- Biomarker Discovery
Background:
- The global tuberculosis (TB) pandemic necessitates novel biomarkers for identifying infectious patients.
- Plasma protein profiles in active pulmonary TB may serve as diagnostic indicators.
- Distinguishing TB from other respiratory infections requires improved diagnostic tools.
Purpose of the Study:
- To identify and validate plasma protein biomarkers for diagnosing pulmonary tuberculosis.
- To differentiate TB cases from healthy individuals and patients with other respiratory infections.
- To assess the potential of these biomarkers for near-patient screening assays.
Main Methods:
- Employed a sensitive tandem mass spectrometry approach to analyze plasma proteins in South African and Peruvian cohorts.
- Utilized bioinformatic analyses, including linear modeling and network correlation, to identify differentially expressed proteins.
- Validated candidate biomarkers in diverse ethnic cohorts using antibody-based proximity extension assays.
Main Results:
- Identified 118 differentially expressed proteins through rigorous bioinformatic analysis.
- Confirmed TB-specific host biomarkers with high sensitivity and specificity.
- A 6-protein panel (FETUB, FCGR3B, LRG1, SELL, CD14, ADA2) effectively differentiated pulmonary TB patients.
Conclusions:
- The 6-protein biomarker panel meets World Health Organization criteria for a TB triage test.
- These novel biomarkers show potential for development into near-patient TB screening assays.
- The findings contribute to closing the case-detection gap in the global TB pandemic.
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