Serum levels of matrix metalloproteinases as prognostic markers for severe dengue with plasma leakage

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.