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

Autor: Goeijenbier M; Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands. Electronic address: m.goeijenbier@erasmusmc.nl., Gasem MH; Department of Medicine, Dr. Kariadi Hospital, Faculty of Medicine, Diponegoro University, Semarang, Indonesia; National Reference Laboratory for Leptospirosis, Dr. Kariadi Hospital, Semarang, Indonesia., Meijers JC; Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Plasma Proteins, Sanquin Research, Amsterdam, The Netherlands., Hartskeerl RA; WHO/FAO/OIE and National Leptospirosis Reference Centre, KIT Biomedical Research, Amsterdam, The Netherlands., Ahmed A; WHO/FAO/OIE and National Leptospirosis Reference Centre, KIT Biomedical Research, Amsterdam, The Netherlands., Goris MG; WHO/FAO/OIE and National Leptospirosis Reference Centre, KIT Biomedical Research, Amsterdam, The Netherlands., Isbandrio B; National Reference Laboratory for Leptospirosis, Dr. Kariadi Hospital, Semarang, Indonesia., Schuller SS; Vetsuisse Faculty, University of Bern, Bern, Switzerland., Osterhaus AD; Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands; ARTEMIS One Health Research Institute, Utrecht, The Netherlands., Martina BE; Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands; ARTEMIS One Health Research Institute, Utrecht, The Netherlands., van Gorp EC; Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands., Nally JE; Bacterial Diseases of Livestock Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, IA, United States., Wagenaar JF; Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands; WHO/FAO/OIE and National Leptospirosis Reference Centre, KIT Biomedical Research, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: The Journal of infection [J Infect] 2015 Oct; Vol. 71 (4), pp. 437-46. Date of Electronic Publication: 2015 Jun 03.
DOI: 10.1016/j.jinf.2015.05.016
Abstrakt: Objectives: 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.
Methods: 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.
Results: 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.
Discussion: Markers of endothelial activation and immune activation were associated with disease severity in leptospirosis patients.
(Copyright © 2015 The British Infection Association. All rights reserved.)
Databáze: MEDLINE
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