Increased shedding of PECAM-1 associated with elevated serum MMP-14 levels as new blood indicators of dengue disease manifestation.

ABSTRACT

OBJECTIVES: Host factors that regulate plasma leakage during severe dengue (SD) are under investigation. While PECAM-1 and MMP-14 have been reported to regulate vascular integrity, their role in dengue pathogenesis remains unexplored. This study aims to assess the association of soluble PECAM-1 and MMP-14 with dengue severity symptoms. PATIENTS AND METHODS: Serum levels of PECAM-1 and MMP-14 were evaluated in dengue (N-25) comprising 10 severe dengue (SD) and 15 non-severe dengue, 10 other febrile illnesses along with healthy controls (N-10) using ELISA. Protein levels were assessed using in vitro models. RESULTS: From febrile to critical phase, a significant increase in PECAM-1 (P≤0.01) & MMP-14 (P≤0.001) levels were observed in SD cases compared to non-severe or other controls. Serum levels of PECAM-1 and MMP 14 were found to be positively (P≤0.001) associated. Soluble PECAM-1 levels of severe defervescence showed a positive correlation (P≤0.001) with plasma leakage and an inverse relationship (P≤0.001) with platelet count. In vitro analysis revealed elevated expression of study proteins in endothelial cells activated with severe serum samples. To the best of our knowledge, this is the first report to explore PECAM-1 or MMP-14 dynamics and their association with dengue severity. CONCLUSION: Higher shedding of sPECAM-1 accompanied with increased levels of MMP-14 is strongly associated with severe dengue. However, the exact role of serum PECAM-1 in disease prognosis requires further studies.