title: Contact-system activation in children with vasculitis.
abstract: BACKGROUND
  The contact system triggers the kallikrein-kinin cascade, liberating bradykinin from high-molecular-weight kininogen. Effectors of the contact system have proinflammatory and vasoactive properties. Vasculitis is a condition characterised by inflammation around vessel walls, leading to secondary tissue damage for which the underlying molecular mechanisms are poorly understood. Our aim was to investigate contact-system activation in children with vasculitis.
  
  
  METHODS
  We compared 17 children, aged 4-19 years, with vasculitis, engaging the skin, joints, intestines, or kidneys, with 21 controls, aged 2-18 years. We analysed proteolysis of high-molecular-weight kininogen by immunoblotting. Plasma bradykinin concentrations were quantified by ELISA. Kidney and skin biopsies were stained in situ for kinins. Concentrations of heparin binding protein (HBP) were quantified by ELISA.
  
  
  RESULTS
  We noted extensive proteolysis of high-molecular-weight kininogen in the plasma of 13 of 17 patients, but in only one of 21 controls (p<0.0001). Bradykinin concentrations were higher in the patients' plasma (median 320 ng/L, range <1-19680) than in plasma from controls (11 ng/L, <1-304; p=0.0004). Patients had local release of kinins at sites of inflammation in kidney and skin biopsies. HBP values were raised in patients (17.4 microg/L, 5.4-237.6) compared with controls (6 microg/L, 2.5-43.4; p=0.008).
  
  
  CONCLUSIONS
  Activation of the contact system could play a part in the pathogenesis of vasculitis, and explain the inflammation, pain, vasodilatation, and oedema seen in patients.
authors.affiliation: Department of Paediatrics, Lund University, Lund, Sweden.
authors.forename: Robin
authors.initials: R
authors.lastname: Kahn
authors.forename: Heiko
authors.initials: H
authors.lastname: Herwald
authors.forename: Werner
authors.initials: W
authors.lastname: Müller-Esterl
authors.forename: Roland
authors.initials: R
authors.lastname: Schmitt
authors.forename: Ann-Christine
authors.initials: AC
authors.lastname: Sjögren
authors.forename: Lennart
authors.initials: L
authors.lastname: Truedsson
authors.forename: Diana
authors.initials: D
authors.lastname: Karpman
mesh_terms: D000293:Adolescent; D000328:Adult; D001920:Bradykinin / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007223:Infant; D007668:Kidney / Q000378:metabolism; D007704:Kininogens / Q000378:metabolism; D008297:Male; D012867:Skin / Q000378:metabolism; D014657:Vasculitis / Q000378:metabolism*
chemical_list: D007704:Kininogens; D001920:Bradykinin