Peer reviewedOpen accessTuberculosis

Inflammatory biomarkers of asymptomatic and symptomatic tuberculosis

Nature Communications·July 25, 2026

Denis Awany, Dominique T. Ariefdien, Simon C. Mendelsohn, Virginie Rozot, Humphrey Mulenga, Sarah Nyangu, Michele Tameris, Tumelo Moloantoa, Austin Katona, Fernanda Maruri, Firdows Noor, Ravindre Panchia, Khuthadzo Hlongwane, Kim Stanley, Yuri F. van der Heijden, Katie Hadley, Andrew- Fiore Gartland, Craig Innes, William Brumskine, Keertan Dheda, Shameem Jaumdally, Tahlia Perumal, Neil Martinson, Al Leslie, Bernard Fourie, Andriëtte Hiemstra, Stephanus T. Malherbe, Gerhard Walzl, Kogieleum Naidoo, Gavin Churchyard, Novel N. Chegou, Timothy R. Sterling, Mark Hatherill, Thomas J. Scriba, Pattamukkil Abraham, Thakiera Allie, Cynthia Baard, Zainab Baig, John Belisle, Nicole Bilek, Gerard Cangelosi, Ace Carstens, Kevyna Chetty, Yolundi Cloete, Marwou de Kock, Gareta Dickman, Charity Dire, Karen Dobos, Stephany Norah Duda, Mzwandile Erasmus, Marina Cruvinel Figueiredo, Marika Flinn, Travis Harris, Ryan Johnson, Farina Karim, Masooda Kaskar, Nobulumko Khomba, Thandeka Khoza, Léanie Kleynhans, Tahira Kootbodien, Andrea Kotze, Belinda A. Kriel, Ané Kruger, Lorraine Lichakane, Ilze Louw, Angelique Luabeya, Candice MacDonald, Lindiwe Madziwa, Lebohang Makhethe, Sandisiwe Mangali, Linda Mbuthini, Carolina Mehaffy, Thabang Moloja, Angelique Mouton, Evans Muchiri, Mbusiseni Ngema, Hlengiwe Nkambule, Onke Nombida, Alaina Olson, Fajwa Opperman, Gregory Ording-Jespersen, Kennedy Otwombe, Will Ramsay, Tracy Richardson, Carmen Segelaar, Jane Shaw, Kimberly Shelton, Justin Shenje, Theresa Smit, Bronwyn Smith, Candice Snyders, Marcia Steyn, Sara Suliman, Floris Swanepoel, Lorraine Thobakgale, Susanne Tonsing, Nicolette Tredoux, Megan Turner, Petrus Tyambetyuv, Habibullah Valley, Lyle van de Berg, Gian van der Spuy, Ilana R. van Rensburg, Johanna E. van Rooyen, Hilary Vansell Riley, Ashley Veldsman, Lindsay Wilson, Rachel C. Wood, Lesley Workman, Heather Zar, Charmaine Abrahams, Hadn Africa, Petri Ahlers, Laudicia Tshenolo Bontsi, Obakeng Peter Booi, Natasja Botes, Mari Cathrin Botha, Samentra Braaf, Sivuyile Buhlungu, Alida Carstens, Nompumelelo Cetywayo, Kgomotso Violet Chauke, Tilagavathy Chinappa, Eva Chung, Michelle Chung, Alessandro Companie, Cara-Mia Corris, Mooketsi Theophillius Cwaile, Thobelani Cwele, Ilse Davids, Isabella Johanna Davies, Emilia De Klerk, Bongani Diamond, Celaphiwe Dlamini, Margareth Erasmus, Elizabeth Filander, Hennie Geldenhuys, Dhineshree Govender, Yolande Gregg, Goodness Khanyisile Gumede, Nonhlanhla Zanele Elsie Gwamanda, Roxane Herling, Andriette Hiemstra, Senzo Ralph Hlathi, Blanchard Mbay Iyemosolo, Zandile Patrica Jali, Ruwiyda Jansen, James Michael Jeleni, Fazlin Kafaar, Christian Mabika Kasongo, Sebaetseng Jeanette Kekana, Xoliswa Kelepu, Justine Khoury, Lucky Sipho Khoza, Gloria Keitumetse Kolobe, Belinda Kriel, Lerato Julia Lekagane, Sheiley Christina Lekotloane, Ilze Jeanette Louw, Andre Loxton, Sarah Teboso Lusale, Elizna Maasdorp, Perfect Tiisetso Maatjie, Kamogelo Fortunate Mabena, Simbarashe Mabwe, Lauren Mactavie, Johanna Thapelo Madikwe, Octavia Mahkosazana Madikwev, Rapontwana Letlhogonolo Maebana, Nomsitho Magawu, Malobisa Sylvester Magwasha, Bhavna Maharaj, Lebohgang Makhete, Vutlhari-I-Vunhenha Fairlord Manzini, Nonhle Bridgette Maphanga, Jabulisiwe Lethabo Maphanga, Isholedi Samuel Maroele, Omphile Petunia Masibi, July Rocky Mathabanzini, Tendamudzimu Ivan Mathode, Ellen Ditaba Matsane, Lungile Mbata, Siyabonga Mbatha, Nyasha Karen Mhandire, Thembisiwe Miga, Nosisa Charity Thandeka Mkhize, Caroline Mkhokho, Neo Hilda Mkwalase, Nondzakazi Mnqonywa, Brenda Matshidiso Modisaotsile, Patricia Pakiso Mokgetsengoane, Selemeng Matseliso Carol Mokone, Kegomoditswe Magdeline Molatlhegi, Thuso Andrew Molefe, Motlatsi Evelyn Molotsi, Tebogo Edwin Montwedi, Boikanyo Dinah Monyemangene, Hellen Mokopi Mooketsi, Atika Moosa, Razia Hassan Moosa, Miriam Moses, Tshplpfelo Mapula Mosito, Ireen Lesebang Mosweu, Banyana Olga Motlagomang, Funeka Nomvula Mthembu, Liesel Muller, Nambitha Nqakala, Ntombozuko Gloria Ntanjana, Sphelele Simo Nzimande, Christel Petersen, Themba Phakathi, Mapule Ozma Phatshwane, Patiswa Plaatjie, Victor Kgothatso Rameetse, Frances Ratangee, Susan Rossouw, Alicia Sato, Kelebogile Magdeline Segaetsho, Ni Ni Sein, Melissa Neo Senne, Sifiso Cornelius Shezi, Thandiwe Yvonne Shezi, Zibuyile Phindile Penlee Sing, Zona Sithetho, Bongiwe Stofile, Sonia Stryers, Liticia Swanepoel, Mando Mmakhora Thaba, Lethabo Collen Theko, Dimakatso Sylvia Tsagae, Petrus Tyambetyu, Elma Van Rooyen, Helen Veldtsman, Mbali Ignatia Zulu

DOI: 10.1038/s41467-026-75909-6
PMID: 42649201
PMCID: —
OpenAlex: W4415678783
Study type: Journal article
Publisher: Springer Science and Business Media LLC
Article type: journal-article
Integrity: current

Why this research matters now

The findings suggest that biomarkers developed for symptomatic tuberculosis triage should not be directly adopted for community-based asymptomatic screening without additional optimization.

Structured evidence summary

Research question

The study examined whether blood transcriptomic and proteomic profiles differ between asymptomatic and symptomatic tuberculosis cases identified through community screening versus health facility triage.

Study design

The study compared blood transcriptomic and proteomic profiles between South African community screening and health facility-based triage cohorts.

Population and setting

Participants were drawn from South African community screening cohorts and health facility-based triage settings.

Main findings

Asymptomatic tuberculosis shared core blood molecular features with symptomatic disease, including upregulation of innate, interferon, and inflammatory pathways and downregulation of lymphocyte pathways. Two distinct sub-clusters among asymptomatic cases were characterized by differences in bacterial burden, interferon-gamma responses, body mass index, and radiographic findings. A novel blood transcriptomic signature for asymptomatic tuberculosis was identified, though diagnostic performance of both transcriptomic and proteomic markers was weaker for asymptomatic than symptomatic disease.

Public-health relevance

The findings suggest that biomarkers developed for symptomatic tuberculosis triage should not be directly adopted for community-based asymptomatic screening without additional optimization.

Important limitations

This summary relies on the supplied single-article abstract and metadata. Full interpretation of study limitations, including details of cohort selection, sample size, validation approaches, and generalizability requires review of the complete published article.

GIDS interpretation

This article would be discoverable through disease-specific queries for tuberculosis, country filters for South Africa, and topic filters for diagnostics or health policy within surveillance platforms that index peer-reviewed infectious disease literature.

Related GIDS surveillance

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Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.

Evidence relationships

This article has 8 auditable classifier relationships to diseases, places, topics, and study design.

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