Host markers to monitor the response to tuberculosis (TB) therapy hold some promise. We evaluated the changes in concentration of Mycobacterium tuberculosis (M.tb)-induced soluble biomarkers during early treatment for predicting short- and long-term treatment outcomes. Whole blood samples from 30 cured and 12 relapsed TB patients from diagnosis, week 1, 2, and 4 of treatment were cultured in the presence of live M.tb for seven days and patients followed up for 24 weeks after the end of treatment. 57 markers were measured in unstimulated and antigen-stimulated culture supernatants using Luminex assays. Top performing multi-variable models at diagnosis using unstimulated values predicted outcome at 24 months after treatment completion with a sensitivity of 75.0% (95% CI, 42.8–94.5%) and specificity of 72.4% (95% CI, 52.8–87.3%) in leave-one-out cross validation. Month two treatment responder classification was correctly predicted with a sensitivity of 79.2% (95% CI, 57.8–92.9%) and specificity of 92.3% (95% CI, 64.0–99.8%). This study provides evidence of the early M.tb-specific treatment response in TB patients but shows that the observed unstimulated marker models are not outperformed by stimulated marker models. Performance of unstimulated predictive host marker signatures is promising and requires validation in larger studies.

用于监测结核病 (TB) 治疗反应的宿主标记物具有一定的前景。我们评估了结核分枝杆菌浓度的变化(M.tb)-在早期治疗期间诱导的可溶性生物标志物，用于预测短期和长期治疗结果。来自诊断、治疗第 1、2 和 4 周的 30 名治愈和 12 名复发结核病患者的全血样本在活结核分枝杆菌存在下培养 7 天，并在治疗结束后对患者进行 24 周随访。使用 Luminex 测定法在未刺激和抗原刺激的培养物上清液中测量了 57 种标记物。使用未刺激值进行诊断时表现最佳的多变量模型预测治疗完成后 24 个月的结果，灵敏度为 75.0%（95% CI，42.8-94.5%），特异性为 72.4%（95% CI，52.8-87.3%）在留一法交叉验证中。正确预测了第二个月的治疗反应者分类，灵敏度为 79.2%（95% CI，57.8–92.9%），特异性为 92。3%（95% CI，64.0–99.8%）。这项研究提供了结核病患者早期结核分枝杆菌特异性治疗反应的证据，但表明观察到的未刺激标记模型的表现并不优于刺激标记模型。未刺激的预测性宿主标记特征的性能很有前途，需要在更大规模的研究中进行验证。