Section of Paediatrics, Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, United Kingdom.
National Public Health Speciality Training Programme, South West, United Kingdom.
Front Immunol. 2021 Mar 2;12:637164. doi: 10.3389/fimmu.2021.637164. eCollection 2021.
Recently, host whole blood gene expression signatures have been identified for diagnosis of tuberculosis (TB). Absolute quantification of the concentrations of signature transcripts in blood have not been reported, but would facilitate diagnostic test development. To identify minimal transcript signatures, we applied a transcript selection procedure to microarray data from African adults comprising 536 patients with TB, other diseases (OD) and latent TB (LTBI), divided into training and test sets. Signatures were further investigated using reverse transcriptase (RT)-digital PCR (dPCR). A four-transcript signature (, and ) measured using RT-dPCR distinguished TB patients from those with OD (area under the curve (AUC) 93.8% (CI 82.2-100%). A three-transcript signature () differentiated TB from LTBI (AUC 97.3%, CI: 93.3-100%), regardless of HIV. These signatures have been validated across platforms and across samples offering strong, quantitative support for their use as diagnostic biomarkers for TB.
最近，已经确定了用于诊断结核病（TB）的宿主全血基因表达特征。尚未报道特征转录本在血液中的浓度的绝对定量，但这将有助于诊断测试的开发。为了鉴定最小的转录本特征，我们应用了一种转录本选择程序，对来自非洲成年人的微阵列数据进行了分析，这些成年人包括 536 名结核病患者、其他疾病（OD）和潜伏性结核病（LTBI）患者，并将其分为训练集和测试集。使用逆转录（RT）-数字 PCR（dPCR）进一步研究了这些特征。使用 RT-dPCR 测量的四个转录本特征（、和）可将结核病患者与 OD 患者区分开来（曲线下面积（AUC）为 93.8%（CI 82.2-100%）。三个转录本特征（）可区分 TB 与 LTBI（AUC 为 97.3%，CI：93.3-100%），无论 HIV 状况如何。这些特征已经在不同平台和不同样本中得到了验证，为其作为结核病诊断生物标志物的应用提供了强有力的定量支持。
