Blood transcriptomic signatures predict poor treatment outcomes in drug-susceptible pulmonary TB in Brazil

OverviewThis is a public, subject-level dataset containing key variables necessary to reconstruct the study findings. A data dictionary is also provided in the README file. This dataset includes all available StandardBiotools Biomark HD microfluidic RT-qPCR data and transcriptomic signature scores for a total of 946 whole blood RNA samples from a subset of study participants enrolled in RePORT-Brazil Cohort A.AbstractBackground: Non-sputum biomarkers to monitor tuberculosis treatment and predict poor outcomes are lacking. We evaluated host-blood transcriptomic signatures for treatment monitoring and prognosis (death, treatment failure, recurrence) in adults with pulmonary tuberculosis. Methods: Adults with culture-confirmed, drug-susceptible pulmonary tuberculosis were enrolled at five Brazilian sites. Whole-blood PAXgene samples were collected at baseline, month 2 (M2), and end of treatment (EoT). Treatment failure was defined as sputum culture positivity at month 5 or later. Participants were followed for 24 months from treatment initiation for clinical or microbiological tuberculosis recurrence. Unfavourable outcomes were matched ~1:3 to recurrence-free cure. Twenty-two published blood transcriptomic signatures were measured by microfluidic RT-qPCR and benchmarked against the WHO Target Product Profile (TPP) criteria. Main results: We matched 263 participants with recurrence-free cure to 33 with treatment failure, 24 who died (tuberculosis/unknown cause), and 9 with recurrence. Signature scores generally declined from baseline to EoT. Multiple signatures measured at baseline and M2 predicted recurrence (AUC range 0.71–0.91), with waning performance when measured at EoT (AUC range 0.42–0.89). Against the WHO TPP, 2/22 signatures met minimum criteria at baseline, 13/22 at M2, and none at EoT. Prediction of treatment failure was poor across timepoints (AUC Conclusions: Blood transcriptomic signatures tracked treatment response and predicted recurrence and death, meeting WHO TPP benchmarks at baseline and M2. These findings support prospective, biomarker-guided trials to individualise tuberculosis therapy—shortening regimens for early responders and intensifying care for high-risk patients.概述：本数据集为公开的受试者水平数据集，包含复现该研究结论所需的全部关键变量。README文件中同步提供了数据字典。本数据集涵盖了来自RePORT-Brazil队列A的部分研究受试者的共计946份全血RNA样本的全部可用StandardBiotools Biomark HD微流控实时定量聚合酶链反应（RT-qPCR）数据与转录组特征评分。 摘要 背景：目前尚无用于监测结核病治疗效果、预测不良预后的非痰液生物标志物。本研究针对成人肺结核患者，评估了宿主血液转录组特征在治疗监测及预后（死亡、治疗失败、复发）评估中的应用价值。 方法：在巴西的5个研究中心招募经培养证实的药物敏感性肺结核成人患者。于基线、第2个月（M2）及治疗结束（EoT）三个时间点采集全血PAXgene样本。治疗失败定义为第5个月及之后痰培养结果呈阳性。受试者自治疗启动后接受为期24个月的随访，以监测临床或微生物学层面的结核病复发情况。将不良预后病例与约1:3比例的无复发治愈病例进行匹配。通过微流控RT-qPCR检测了22种已发表的血液转录组特征，并以世界卫生组织（WHO）目标产品概况（Target Product Profile, TPP）标准作为基准开展性能评估。 主要结果：本研究共匹配得到263例无复发治愈病例，以及33例治疗失败病例、24例死亡病例（死因归因于结核病/未知原因）与9例复发病例。特征评分普遍从基线至治疗结束呈下降趋势。在基线及第2个月检测的多种特征可预测结核病复发（受试者工作特征曲线下面积[AUC]范围为0.71~0.91），而在治疗结束时检测的特征预测性能有所衰减（AUC范围为0.42~0.89）。参照WHO TPP标准，22种特征中有2种在基线时达到最低标准，13种在第2个月时达标，治疗结束时无一种特征达标。各时间点对治疗失败的预测效果均较差。 结论：血液转录组特征可追踪治疗应答情况，并可预测结核病复发与死亡，在基线及第2个月时达到WHO TPP基准标准。上述研究结果支持开展以生物标志物为导向的前瞻性试验，以实现结核病治疗的个体化——为早期应答患者缩短治疗疗程，并为高风险患者强化治疗护理。