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Contact-system activation in children with vasculitis.
Robin Kahn1, Heiko Herwald, Werner Müller-Esterl
1Department of Paediatrics, Lund University, Lund, Sweden.
Lancet (London, England)
|September 21, 2002
Summary
Children with vasculitis show activation of the contact system, indicated by increased bradykinin levels. This suggests the contact system plays a role in vasculitis pathogenesis and symptoms like inflammation and swelling.
Area of Science:
- Immunology
- Pathophysiology
- Pediatrics
Background:
- The contact system initiates the kallikrein-kinin cascade, releasing bradykinin.
- Contact system components possess proinflammatory and vasoactive properties.
- Vasculitis involves vessel wall inflammation with poorly understood molecular mechanisms.
Purpose of the Study:
- To investigate contact system activation in pediatric vasculitis patients.
- To explore the link between contact system activation and vasculitis symptoms.
Main Methods:
- Compared 17 children with vasculitis to 21 healthy controls.
- Analyzed high-molecular-weight kininogen proteolysis via immunoblotting.
- Quantified plasma bradykinin and heparin binding protein (HBP) using ELISA; stained biopsies for kinins.
Main Results:
- Extensive high-molecular-weight kininogen proteolysis observed in 13/17 patients vs. 1/21 controls (p<0.0001).
- Significantly higher plasma bradykinin concentrations in patients (median 320 ng/L) vs. controls (11 ng/L) (p=0.0004).
- Elevated HBP levels in patients (17.4 microg/L) vs. controls (6 microg/L) (p=0.008); local kinin release in inflamed tissues.
Conclusions:
- Contact system activation is implicated in vasculitis pathogenesis.
- This activation may explain inflammation, pain, vasodilation, and edema in vasculitis patients.
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