Pavan Kumar Nathella, Hissar Syed, Nancy Arul, Thiruvengadam Kannan, Banurekha Velayuthum V, Balaji Sarath, Elilarasi S, Gomathi N S, Ganesh J, Aravind M A, Baskaran Dhanaraj, Swaminathan Soumya, Babu Subash
ICMR-National Institute for Research in Tuberculosis, Chennai 600031, India.
National Institutes of Health, National Institute for Research in Tuberculosis-International Center for Excellence in Research, Chennai 600031, India.
Diseases. 2025 May 27;13(6):171. doi: 10.3390/diseases13060171.
Diagnosing tuberculosis (TB) in children presents significant challenges, necessitating the identification of reliable biomarkers for accurate diagnosis. In this study, we investigated plasma matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) as potential diagnostic markers. A prospective case-control study involved 167 children classified into confirmed TB, unconfirmed TB, and unlikely TB control groups. Plasma levels of MMPs (MMP 1, 2, 3, 7, 8, 9, 12, and 13) and TIMPs (TIMP 1, 2, 3, and 4) were measured using multiplex assays. Elevated baseline levels of MMP-1, MMP-2, MMP-7, MMP-9, TIMP-1, TIMP-2, TIMP-3, and TIMP-4 were observed in active TB cases compared to unlikely TB controls. Receiver operating characteristics (ROC) analysis identified MMP-1, MMP-2, MMP-9, and TIMP-1 as potential biomarkers with over 80% sensitivity and specificity. A three-MMP signature (MMP-1, MMP-2, and MMP-9) demonstrated 100% sensitivity and specificity. The findings suggest that a baseline MMP signature could serve as an accurate biomarker for diagnosing pediatric TB, enabling early intervention and effective management.
诊断儿童结核病面临重大挑战,因此需要识别可靠的生物标志物以进行准确诊断。在本研究中,我们调查了血浆基质金属蛋白酶(MMPs)和金属蛋白酶组织抑制剂(TIMPs)作为潜在诊断标志物的情况。一项前瞻性病例对照研究纳入了167名儿童,他们被分为确诊结核病组、未确诊结核病组和疑似非结核病对照组。使用多重检测法测量血浆中MMPs(MMP 1、2、3、7、8、9、12和13)和TIMPs(TIMP 1、2、3和4)的水平。与疑似非结核病对照组相比,活动性结核病病例的MMP-1、MMP-2、MMP-7、MMP-9、TIMP-1、TIMP-2、TIMP-3和TIMP-4基线水平升高。受试者工作特征(ROC)分析确定MMP-1、MMP-2、MMP-9和TIMP-1为潜在生物标志物,其敏感性和特异性超过80%。一个由三种MMP组成的特征组合(MMP-1、MMP-2和MMP-9)显示出100%的敏感性和特异性。研究结果表明,基线MMP特征组合可作为诊断儿童结核病的准确生物标志物,有助于早期干预和有效管理。