Neutrophil proteins as potential biomarkers for a sputum-based tuberculosis screening test
Significant increases in all proteins were detectable in sputum from clinic-diagnosed TB participants relative to symptomatic controls. Performance approached the WHO target product profile for a TB triage test, with ROC AUCs reaching 0.866 (with a 95% confidence interval of 0.7683 - 0.9633) in the case of S100A8/A9. Sputum protein levels did not correlate with bacterial burden and did not consistently decrease following one month of drug therapy. Only PDL-1 was detectable in mouth swab samples. Sputum neutrophil proteins tended to be elevated in participants with asymptomatic community diagnosed TB, as compared to asymptomatic community controls within the Vukuzazi cohort using a sample size of 42 participants, although this was not significant. This study provides a proof of principle that neutrophil proteins can be easily measured in standard sputum samples and have potential as a screening test for TB. However, more work is needed to explore whether this approach, using these three neutrophil proteins, can meet the WHO target product profile for a triage test worth developing further.
Authors
- Mark A. Chambers (ORCID: https://orcid.org/0000-0002-8073-8069)
- Ayanda Shabangu
- Matilda Mazibuko
- Stephanus T. Malherbe (ORCID: https://orcid.org/0000-0002-7563-8231)
- Mark Hatherill (ORCID: https://orcid.org/0000-0003-3491-1809)
- Bronwyn Smith
- Ilana C. van Rensburg
- Zoey Mhlane
- Gerhard Walzl (ORCID: https://orcid.org/0000-0003-2487-125X)
- Mahomed‐Yunus S. Moosa (ORCID: https://orcid.org/0000-0001-6191-4023)
- Kim Stanley
- Emily Wong
- Nelita du Plessis (ORCID: https://orcid.org/0000-0001-7881-925X)
- Alasdair J. Leslie (ORCID: https://orcid.org/0000-0003-2538-6467)
- Andriëtte Hiemstra
- Timothy R. Sterling (ORCID: https://orcid.org/0000-0002-4822-6979)
- Belinda Kriel
- Lindiwe Madziwa
- Sashen Moodley
- Farina Karim
- Monjurul Hoque
Institutions
- South African Medical Research Council (ZA)
- University of the Witwatersrand (ZA)
- Vanderbilt University (US)
- Massachusetts General Hospital (US)
- South African Tuberculosis Vaccine Initiative (ZA)
- Africa Health Research Institute (ZA)
- Institute of Infection and Immunity (CA)
- University College London (GB)
- University of KwaZulu-Natal (ZA)
Publication Details
- Journal
- Frontiers in Immunology
- Published
- 2025-10-20
- DOI
- https://doi.org/10.3389/fimmu.2025.1636909
- Primary Topic
- Tuberculosis Research and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- CRDF Global
- South African Medical Research Council
- Universiteit Stellenbosch
- Medical Research Council