Inflammatory biomarkers of asymptomatic and symptomatic tuberculosis
A large proportion of individuals with tuberculosis (TB) are asymptomatic. The biological and inflammatory underpinnings of asymptomatic TB are unknown and may differ from symptomatic TB. We characterised blood transcriptomic and proteomic profiles in South African community screening vs. health facility-based triage cohorts. Asymptomatic TB shared core transcriptomic and proteomic features with symptomatic TB, including upregulation of innate, interferon and inflammatory pathways and downregulation of T and B cell pathways. Integration of transcriptomic and proteomic data from asymptomatic TB individuals identified two distinct sub-clusters characterized by higher or lower bacterial burden, blood IFN-γ responses, BMI, and chest radiographic abnormalities, suggesting different disease severity. We identified a new blood transcriptomic signature of asymptomatic TB. However, diagnostic performance of transcriptomic and proteomic markers was weaker for asymptomatic TB than symptomatic TB, suggesting that policy development for community-based, asymptomatic TB screening should not adopt biomarkers developed for symptomatic TB triage without further optimization.
Authors
- Stephanus T. Malherbe (ORCID: https://orcid.org/0000-0002-7563-8231)
- Mark Hatherill (ORCID: https://orcid.org/0000-0003-3491-1809)
- Katie Hadley
- Tumelo Moloantoa
- Fernanda Maruri (ORCID: https://orcid.org/0000-0001-9533-8239)
- Yuri F. van der Heijden (ORCID: https://orcid.org/0000-0001-7631-9796)
- Humphrey Mulenga (ORCID: https://orcid.org/0000-0002-2030-0751)
- Gavin Churchyard (ORCID: https://orcid.org/0000-0002-4269-3699)
- Firdows Noor
- Novel N. Chegou (ORCID: https://orcid.org/0000-0002-8690-1699)
- Craig Innes (ORCID: https://orcid.org/0000-0002-6872-5687)
- Tahlia Perumal (ORCID: https://orcid.org/0000-0003-0679-5804)
- Andrew Fioré-Gartland (ORCID: https://orcid.org/0000-0001-7627-2166)
- Simon C. Mendelsohn (ORCID: https://orcid.org/0000-0002-4054-2766)
- Michèle Tameris (ORCID: https://orcid.org/0000-0002-7983-7203)
- Kim Stanley
- Khuthadzo Hlongwane (ORCID: https://orcid.org/0000-0002-0882-9599)
- Ravindre Panchia (ORCID: https://orcid.org/0000-0002-3601-0839)
- Thomas J. Scriba (ORCID: https://orcid.org/0000-0002-0641-1359)
- Denis Awany (ORCID: https://orcid.org/0000-0001-8379-814X)
- Keertan Dheda (ORCID: https://orcid.org/0000-0001-7709-5341)
- Kogieleum Naidoo (ORCID: https://orcid.org/0000-0002-8874-6661)
- Virginie Rozot (ORCID: https://orcid.org/0000-0001-9757-1501)
- William Brumskine (ORCID: https://orcid.org/0000-0002-1092-9919)
- Shameem Z. Jaumdally (ORCID: https://orcid.org/0000-0003-0316-7087)
- Andriëtte Hiemstra
- Timothy R. Sterling (ORCID: https://orcid.org/0000-0002-4822-6979)
- Bernard Fourie
- Sarah Nyangu
- W Gerhard
- Austin Katona
- Al Leslie
- Dominique T Ariefdien
Institutions
- South African Medical Research Council (ZA)
- University of Cape Town (ZA)
- University of California, San Francisco (US)
- University of the Witwatersrand (ZA)
- University of Washington (US)
- Stellenbosch University (ZA)
- Centre for the AIDS Programme of Research in South Africa (ZA)
- Fred Hutch Cancer Center (US)
- London School of Hygiene & Tropical Medicine (GB)
- South African Tuberculosis Vaccine Initiative (ZA)
- Aurum Institute (ZA)
- Africa Health Research Institute (ZA)
- Perinatal HIV Research Unit (ZA)
- University College London (GB)
- Seattle University (US)
- University of Pretoria (ZA)
- Vanderbilt University Medical Center (US)
- Colorado State University (US)
- University of KwaZulu-Natal (ZA)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-07-25
- DOI
- https://doi.org/10.1038/s41467-026-75909-6
- Primary Topic
- Tuberculosis Research and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Bill and Melinda Gates Foundation
- CRDF Global
- Vanderbilt University
- South African Medical Research Council
- Universiteit Stellenbosch
- University of Cape Town
- National Institutes of Health
- Medical Research Council