Inflammatory Biomarkers of Asymptomatic and Symptomatic Tuberculosis.
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Awany Denis, Ariefdien Dominique T, Mendelsohn Simon C, Rozot Virginie, Mulenga Humphrey, Nyangu Sarah, Tameris Michele, Moloantoa Tumelo, Katona Austin, Maruri Fernanda, Noor Firdows, Panchia Ravindre, Hlongwane Khuthadzo, Stanley Kim, van der Heijden Yuri F, Hadley Katie, Gartland Andrew-Fiore, Innes Craig, Brumskine William, Dheda Keertan, Jaumdally Shameem, Perumal Tahlia, Martinson Neil, Leslie Al, Fourie Bernard, Hiemstra Andriëtte, Malherbe Stephanus T, Walzl Gerhard, Naidoo Kogieleum, Churchyard Gavin, Chegou Novel N, Sterling Timothy R, Hatherill Mark, Scriba Thomas J
Аннотация
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.