TY - JOUR
T1 - Markers of endothelial cell activation and immune activation are increased in patients with severe leptospirosis and associated with disease severity
AU - Goeijenbier, Marco
AU - Gasem, M. Hussein
AU - Meijers, Joost C. M.
AU - Hartskeerl, Rudy A.
AU - Ahmed, Ahmed
AU - Goris, Marga G. A.
AU - Isbandrio, Bambang
AU - Schuller, Simone S.
AU - Osterhaus, Albert D. M. E.
AU - Martina, Byron E. E.
AU - van Gorp, Eric C. M.
AU - Nally, Jarlath E.
AU - Wagenaar, Jiri F. P.
PY - 2015
Y1 - 2015
N2 - Previous 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. Prospective 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. Plasma 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. Markers of endothelial activation and immune activation were associated with disease severity in leptospirosis patients
AB - Previous 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. Prospective 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. Plasma 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. Markers of endothelial activation and immune activation were associated with disease severity in leptospirosis patients
U2 - https://doi.org/10.1016/j.jinf.2015.05.016
DO - https://doi.org/10.1016/j.jinf.2015.05.016
M3 - Article
C2 - 26048204
SN - 0163-4453
VL - 71
SP - 437
EP - 446
JO - Journal of Infection
JF - Journal of Infection
IS - 4
ER -