Jenum Synne, Dhanasekaran S, Lodha Rakesh, Mukherjee Aparna, Kumar Saini Deepak, Singh Sarman, Singh Varinder, Medigeshi Guruprasad, Haks Marielle C, Ottenhoff Tom H M, Doherty Timothy Mark, Kabra Sushil K, Ritz Christian, Grewal Harleen M S
Department of Global Public Health and Primary Care, University of Bergen, and Department of Medical Microbiology, Vestre Viken Hospital Trust, Drammen, Norway.
Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, N-5021, Norway.
Sci Rep. 2016 Jan 4;6:18520. doi: 10.1038/srep18520.
The World Health Organization (WHO) calls for an accurate, rapid, and simple point-of-care (POC) test for the diagnosis of pediatric tuberculosis (TB) in order to make progress "Towards Zero Deaths". Whereas the sensitivity of a POC test based on detection of Mycobacterium tuberculosis (MTB) is likely to have poor sensitivity (70-80% of children have culture-negative disease), host biomarkers reflecting the on-going pathological processes across the spectrum of MTB infection and disease may hold greater promise for this purpose. We analyzed transcriptional immune biomarkers direct ex-vivo and translational biomarkers in MTB-antigen stimulated whole blood in 88 Indian children with intra-thoracic TB aged 6 months to 15 years, and 39 asymptomatic siblings. We identified 12 biomarkers consistently associated with either clinical groups "upstream" towards culture-positive TB on the TB disease spectrum (CD14, FCGR1A, FPR1, MMP9, RAB24, SEC14L1, and TIMP2) or "downstream" towards a decreased likelihood of TB disease (BLR1, CD3E, CD8A, IL7R, and TGFBR2), suggesting a correlation with MTB-related pathology and high relevance to a future POC test for pediatric TB. A biomarker signature consisting of BPI, CD3E, CD14, FPR1, IL4, TGFBR2, TIMP2 and TNFRSF1B separated children with TB from asymptomatic siblings (AUC of 88%).
世界卫生组织（WHO）呼吁开展准确、快速且简便的即时检测（POC），用于诊断儿童结核病（TB），以推动实现“零死亡”目标。鉴于基于检测结核分枝杆菌（MTB）的即时检测的灵敏度可能较低（70-80%的儿童患有培养阴性疾病），反映MTB感染和疾病全过程中正在进行的病理过程的宿主生物标志物可能更有前景。我们分析了88名年龄在6个月至15岁的印度胸腔内结核患儿以及39名无症状同胞的MTB抗原刺激全血中的转录免疫生物标志物（直接体外）和转化生物标志物。我们确定了12种生物标志物，它们在结核病谱上与临床组“上游”（即培养阳性结核病方向）（CD14、FCGR1A、FPR1、MMP9、RAB24、SEC14L1和TIMP2）或“下游”（即结核病患病可能性降低方向）（BLR1、CD3E、CD8A、IL7R和TGFBR2）始终相关，这表明与MTB相关病理存在相关性，并且与未来儿童结核病即时检测高度相关。由BPI、CD3E、CD14、FPR1、IL4、TGFBR2、TIMP2和TNFRSF1B组成的生物标志物特征可将结核病患儿与无症状同胞区分开来（曲线下面积为88%）。
