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
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
bioRxiv. 2025 Oct 29:2025.10.26.684319. doi: 10.1101/2025.10.26.684319.
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.
很大一部分肺结核（TB）患者没有症状。无症状肺结核的生物学和炎症基础尚不清楚，可能与有症状肺结核不同。我们对南非社区筛查队列与基于医疗机构分诊队列的血液转录组和蛋白质组图谱进行了特征分析。无症状肺结核与有症状肺结核具有共同的核心转录组和蛋白质组特征，包括先天免疫、干扰素和炎症途径的上调以及T细胞和B细胞途径的下调。对无症状肺结核个体的转录组和蛋白质组数据进行整合，确定了两个不同的亚群，其特征是细菌载量、血液干扰素-γ反应、体重指数和胸部X线异常情况较高或较低，这表明疾病严重程度不同。我们确定了一种新的无症状肺结核血液转录组特征。然而，转录组和蛋白质组标志物对无症状肺结核的诊断性能比对有症状肺结核的诊断性能要弱，这表明基于社区的无症状肺结核筛查政策制定不应在未进一步优化的情况下采用为有症状肺结核分诊而开发的生物标志物。
