Contact-system activation in children with vasculitis.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/110234
- author
- Kahn, Robin LU ; Herwald, Heiko LU ; Müller-Esterl, Werner ; Schmitt, Roland LU ; Sjögren, Ann-Christine LU ; Truedsson, Lennart LU and Karpman, Diana LU
- organization
- publishing date
- 2002
- type
- Contribution to journal
- publication status
- published
- subject
- in
- The Lancet
- volume
- 360
- issue
- 9332
- pages
- 535 - 541
- publisher
- Elsevier
- 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
- 2016-04-01 12:00:36
- date last changed
- 2022-03-13 03:55:40
@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<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.}}, 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}}, series = {{The Lancet}}, title = {{Contact-system activation in children with vasculitis.}}, url = {{http://dx.doi.org/10.1016/S0140-6736(02)09743-X}}, doi = {{10.1016/S0140-6736(02)09743-X}}, volume = {{360}}, year = {{2002}}, }