Markers of endothelial cell activation and immune activation are increased in patients with severe leptospirosis and associated with disease severity

- sE-selectin and VWF levels are strongly elevated in severe leptospirosis patients. sE-selectin is elevated in non-survivors.
- Endothelial cells exposed to live virulent Leptospira in vitro, show an increased surface Von Willebrand factor expression.
- Levels of soluble Fas Ligand and soluble IL-2 receptor both are strongly associated with mortality.
- sIL-2r levels are increased in patients that develop bleeding and positively correlated with duration of hospital admission.

SummaryObjectivesPrevious studies concluded that haemorrhage is one of the most accurate prognostic factors of mortality in leptospirosis. Therefore, endothelial cell activation was investigated in relation to disease severity in severe leptospirosis.MethodsProspective cohort study of severe leptospirosis patients. Plasma levels of sE-selectin and Von Willebrand factor (VWF) were determined. Consequently, an in vitro endothelial cell model was used to assess endothelial activation after exposure to virulent Leptospira. Finally, immune activation, as a potential contributing factor to endothelial cell activation, was determined by soluble IL2-receptor (sIL-2r) and soluble Fas-ligand (sFasL) levels.ResultsPlasma levels of sE-selectin and VWF strongly increased in patients compared to healthy controls. Furthermore, sE-selectin was significantly elevated (203 ng/ml vs. 157 ng/ml, p < 0.05) in survivors compared to non-survivors. Endothelial cells exposed to virulent Leptospira showed increased VWF expression. E-selectin and ICAM-1 expression did not change. Immunohistochemistry revealed the presence of intracellular Leptospira and qPCR suggested replication. In vivo analysis showed that increased levels of sFasL and sIL-2r were both strongly associated with mortality. Furthermore sIL-2r levels were increased in patients that developed bleeding and significantly correlated to duration of hospital stay.DiscussionMarkers of endothelial activation and immune activation were associated with disease severity in leptospirosis patients.