State Level Viral Research and Diagnostic Laboratory (VRDL), Department of Virology, King Institute of Preventive Medicine and Research, Chennai 600 032, India.
Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India.
Exp Mol Pathol. 2022 Oct;128:104821. doi: 10.1016/j.yexmp.2022.104821. Epub 2022 Jul 28.
Plasma leakage is a major pathogenic manifestation of severe dengue and is a precursor of life-threatening complications associated with dengue. Accumulating evidence indicates the role of Matrix Metalloproteinases (MMPs) in mediating vascular permeability and plasma leakage following induction by the dengue virus. This study aims to investigate the utility of MMP-2, MMP-3, and MMP-9 in predicting the severity of dengue infection and further explore the relationship of these markers with the pathogenic factors associated with plasma leakage.
The dengue-positive subjects were classified into mild and severe dengue groups based on the manifestation of warning signs. The samples in each group and healthy controls were quantified for basic laboratory characteristics. The levels of MMP-2, MMP-3, MMP-9, and Macrophage migration inhibitory factor (MIF) were estimated in all serum samples using a multiplex bead-based assay.
MMP-2 and MMP-9 were markedly elevated in severe dengue patients compared to mild dengue patients and healthy controls. No alteration in the circulating levels of MMP-3 was observed between the study groups. ROC curve analysis indicated that MMP-2 and MMP-9 exhibited good potential for predicting severe dengue. Notably, an increase in MMP-9 was associated with increased MIF and Hematocrit levels in severe dengue patients.
MMP-2 and MMP-9 could serve as prognostic biomarkers for severe dengue. These findings also identify the association of MMP-9 with markers of plasma leakage, thereby encouraging further studies to explore the therapeutic potential of targeting MMP-9 in managing plasma leakage in severe dengue.
血浆渗漏是重症登革热的主要发病表现，也是与登革热相关的危及生命的并发症的前兆。越来越多的证据表明基质金属蛋白酶（MMPs）在介导血管通透性和登革病毒诱导的血浆渗漏方面发挥作用。本研究旨在探讨 MMP-2、MMP-3 和 MMP-9 在预测登革热感染严重程度中的应用价值，并进一步探讨这些标志物与与血浆渗漏相关的致病因子的关系。
根据预警症状将登革热阳性患者分为轻症和重症登革热组。对每组样本和健康对照组进行基本实验室特征的定量分析。使用基于多重微珠的检测方法，对所有血清样本中的 MMP-2、MMP-3、MMP-9 和巨噬细胞移动抑制因子（MIF）水平进行估计。
与轻症登革热患者和健康对照组相比，重症登革热患者的 MMP-2 和 MMP-9 明显升高。研究组之间循环 MMP-3 水平没有变化。ROC 曲线分析表明，MMP-2 和 MMP-9 对预测重症登革热具有良好的潜力。值得注意的是，重症登革热患者 MMP-9 的增加与 MIF 和红细胞压积水平的升高相关。
MMP-2 和 MMP-9 可作为重症登革热的预后生物标志物。这些发现还确定了 MMP-9 与血浆渗漏标志物的关联，从而鼓励进一步研究探索靶向 MMP-9 治疗重症登革热中血浆渗漏的治疗潜力。
