Clinical correlations of plasma sphingosine-1-phosphate and sphingolipid key enzymes in severe dengue using laboratory and machine learning approach.

BACKGROUND

Sphingolipids are crucial for vascular integrity and cellular homeostasis, with recent studies highlighting their role in viral diseases.

OBJECTIVES

The study aimed to assess the plasma levels of sphingolipids, specifically Sphingosine-1-phosphate (S1P) and the key enzymes of sphingolipid metabolism: Sphingomyelin synthase (SMS1), Ceramide Kinase (CERK) and acid ceramidase (ASAH1) and its association with clinical outcomes of dengue.

METHODS

This prospective cohort study had 102 dengue cases with 17 severe dengue (SD), 33 dengue with warning signs (DWW), 52 dengue without warning signs (DWOW) along with 10 each from other febrile illnesses and healthy controls. Blood was collected across febrile, defervescence, and convalescence phases. Plasma levels of S1P and the enzymes were measured using ELISA, mRNA using qRT-PCR. Predictive efficacy was determined using Support vector machine (SVM) models.

RESULTS

Study showed a significant reduction in S1P levels across all dengue forms during febrile phases, with further decline in SD during the critical phase (P < 0.05).mRNA levels of the enzymes were increasing during critical phase (P ≤ 0.001) with no significant difference noted in their respective protein levels. S1P and SMS1 levels correlated significantly with clinical severity indicators, including hematocrit, albumin, platelet count, and liver enzymes. SVM analysis identified CERK levels along with platelet count, HCT, and ALT as markers with high predictive accuracy for dengue severity.

CONCLUSION

The study reports an association of sphingolipids with dengue virulence, emphasizing the role of S1P metabolism in disease progression and plasma leakage, and highlighting the potential of targeting sphingolipids in managing severe dengue.