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Contact-system activation in children with vasculitis.

Kahn, Robin LU ; Herwald, Heiko LU ; Müller-Esterl, Werner; Schmitt, Roland LU ; Sjögren, Ann-Christine LU ; Truedsson, Lennart LU and Karpman, Diana LU (2002) In The Lancet 360(9332). p.535-541
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... (More)
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. FINDINGS: 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). INTERPRETATION: 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The Lancet
volume
360
issue
9332
pages
535 - 541
publisher
Elsevier Limited
external identifiers
  • pmid:12241658
  • wos:000177512800012
  • scopus:0037125571
ISSN
1474-547X
DOI
10.1016/S0140-6736(02)09743-X
language
English
LU publication?
yes
id
a373b64a-ab1c-4c44-a64f-8c33405e914a (old id 110234)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12241658&dopt=Abstract
date added to LUP
2007-07-19 12:14:57
date last changed
2017-08-27 04:00:32
@article{a373b64a-ab1c-4c44-a64f-8c33405e914a,
  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. FINDINGS: 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&lt;0.0001). Bradykinin concentrations were higher in the patients' plasma (median 320 ng/L, range &lt;1-19680) than in plasma from controls (11 ng/L, &lt;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). INTERPRETATION: 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.},
  author       = {Kahn, Robin and Herwald, Heiko and Müller-Esterl, Werner and Schmitt, Roland and Sjögren, Ann-Christine and Truedsson, Lennart and Karpman, Diana},
  issn         = {1474-547X},
  language     = {eng},
  number       = {9332},
  pages        = {535--541},
  publisher    = {Elsevier Limited},
  series       = {The Lancet},
  title        = {Contact-system activation in children with vasculitis.},
  url          = {http://dx.doi.org/10.1016/S0140-6736(02)09743-X},
  volume       = {360},
  year         = {2002},
}