Ning Bo, Chandra Sutapa, Pan Yongchun, Sharan Riti, Ha Ngan, Singh Sanjay, Portillo Varela Alexandra, Li Lin, Wu Qingli, Kay Alexander, Maphalala Gugu P, Adu-Gyamfi Clement, Carrero Longlax Santiago, Mandalakas Anna M, Mehra Smriti, Lyon Christopher J, Graviss Edward A, DiNardo Andrew R, Hu Tony
Center for Cellular and Molecular Diagnostics, Tulane University School of Medicine, New Orleans, LA, USA.
Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA, USA.
Nat Biomed Eng. 2025 Jun 27. doi: 10.1038/s41551-025-01441-5.
Interferon-gamma release assays (IGRAs) that evaluate an individual's T-cell activation response to Mycobacterium tuberculosis (M.tb)-specific peptides serve an important role in diagnosing tuberculosis (TB). However, there are substantial challenges to the use of IGRAs in resource-limited settings. Further, IGRA diagnostic performance can also be compromised in anergic individuals. Here we describe a microfluidic chip-based antigen-specific T-cell response assay (ASTRA) that automates the detection of M.tb-specific T-cell activation responses to facilitate screening for latent M.tb infection and TB. We observe that ASTRA demonstrates high specificity for M.tb infection in independent patient cohorts. Compared with IGRA, ASTRA shows greater diagnostic sensitivity in individuals with HIV-1 co-infections (93.8% versus 67%), comparable diagnostic sensitivity in HIV-negative individuals (92.8%) and faster detection (4 h versus 24-48 h). We also find that a self-powered ASTRA chip that analysed microsample (~25 μl) whole-blood samples produced comparable results. ASTRA holds the potential to facilitate efforts to control the global TB epidemic and serve as a versatile platform for analysing T-cell responses across various infectious diseases and immunotherapeutic interventions.
评估个体对结核分枝杆菌（M.tb）特异性肽的T细胞激活反应的干扰素-γ释放试验（IGRAs）在结核病（TB）诊断中发挥着重要作用。然而，在资源有限的环境中使用IGRAs存在重大挑战。此外，无反应个体的IGRA诊断性能也可能受到影响。在此，我们描述了一种基于微流控芯片的抗原特异性T细胞反应测定法（ASTRA），该方法可自动检测M.tb特异性T细胞激活反应，以促进对潜伏性M.tb感染和TB的筛查。我们观察到，ASTRA在独立患者队列中对M.tb感染表现出高特异性。与IGRA相比，ASTRA在合并HIV-1感染的个体中显示出更高的诊断敏感性（93.8%对67%）在HIV阴性个体中具有相当的诊断敏感性（92.8%），且检测速度更快（4小时对24-48小时）。我们还发现，分析微量样本（约25μl）全血样本的自供电ASTRA芯片产生了可比的结果。ASTRA有潜力促进全球结核病流行的控制工作，并作为一个通用平台用于分析各种传染病和免疫治疗干预中的T细胞反应。
