title: Decreased expression of serum and microvascular vascular endothelial growth factor receptor-2 in meningococcal sepsis*.
abstract: OBJECTIVE
  To determine the skin microvessel expression of vascular endothelial growth factor receptor 2 and serum-soluble vascular endothelial growth factor receptor 2 levels in children with meningococcal sepsis.
  
  
  METHODS
  Observational study.
  
  
  METHODS
  Two tertiary academic children hospital PICUs.
  
  
  METHODS
  Children with meningococcal sepsis.
  
  
  METHODS
  Skin biopsy and blood sample collection.
  
  
  RESULTS
  Determination of skin microvessel vascular endothelial growth factor receptor 2 expression in skin biopsies by immunohistochemistry and measurement of serum-soluble vascular endothelial growth factor receptor 2 by enzyme-linked immunosorbent assay. Percentage of vascular endothelial growth factor receptor 2-positive skin microvessels and the staining intensity were significantly lower in children with meningococcal sepsis (n = 10) compared to controls (7.6% ± 8.8% vs 44.6% ± 39.2%; p = 0.009 and 0.7% ± 0.7% vs 1.7% ± 1.1%; p = 0.033, respectively). In addition, circulating serum levels of soluble vascular endothelial growth factor receptor 2 were decreased in sepsis (8,148 ± 1,140 pg/mL vs 13,414 ± 2,692 pg/mL; p < 0.001). Serum-soluble vascular endothelial growth factor receptor 2 levels (n = 28) were inversely correlated with Pediatric Risk of Mortality III score (r = -0.43; p = 0.023) and more decreased in nonsurvivors compared to survivors (5,640 ± 1,940 pg/mL vs 7,378 ± 2,336 pg/mL; p = 0.037).
  
  
  CONCLUSIONS
  Microvascular expression of vascular endothelial growth factor receptor 2 and serum-soluble vascular endothelial growth factor receptor 2 levels are decreased in children with sepsis. Serum-soluble vascular endothelial growth factor receptor 2 levels are inversely correlated with disease severity indicated by Pediatric Risk of Mortality III score and survival. Decreased vascular endothelial growth factor receptor 2 expression may hinder natural recovery from sepsis-associated microvascular injury and the effectiveness of therapeutic strategies targeting vascular endothelial growth factor-vascular endothelial growth factor receptor 2 signaling in sepsis patients.
authors.affiliation: 1Department of Pediatrics, Radboud University Medical Centre, Nijmegen, The Netherlands. 2The Nijmegen Institute for Infection, Inflammation, and Immunity, Radboud University Medical Centre, Nijmegen, The Netherlands. 3Department of Immunology, Erasmus Medical Centre, Rotterdam, The Netherlands. 4Department of Dermatology, Erasmus Medical Centre, Rotterdam, The Netherlands. 5Pediatric Intensive Care Unit, University Medical Centre Utrecht, Utrecht, The Netherlands. 6Department of Pediatric Infectious Diseases and Immunology, Erasmus Medical Centre, Rotterdam, The Netherlands. 7Pediatric Intensive Care Unit, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: van der Flier
authors.forename: Ewout M
authors.initials: EM
authors.lastname: Baerveldt
authors.forename: Annemieke
authors.initials: A
authors.lastname: Miedema
authors.forename: Nico G
authors.initials: NG
authors.lastname: Hartwig
authors.forename: Jan A
authors.initials: JA
authors.lastname: Hazelzet
authors.forename: Marieke
authors.initials: M
authors.lastname: Emonts
authors.forename: Ronald
authors.initials: R
authors.lastname: de Groot
authors.forename: Errol P
authors.initials: EP
authors.lastname: Prens
authors.forename: Adrianus J
authors.initials: AJ
authors.lastname: van Vught
authors.forename: Nicolaas J
authors.initials: NJ
authors.lastname: Jansen
mesh_terms: D000046:Academic Medical Centers; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006305:Health Status Indicators; D006801:Humans; D007223:Infant; D015278:Intensive Care Units, Pediatric / Q000706:statistics & numerical data*; D008297:Male; D008589:Meningococcal Infections / Q000097:blood* / Q000401:mortality; D055806:Microvessels; D018805:Sepsis / Q000097:blood* / Q000401:mortality; D012867:Skin / Q000098:blood supply*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood*
chemical_list: D040301:Vascular Endothelial Growth Factor Receptor-2