Contact-system activation in children with vasculitis
Autor: | Ann-Christine Sjögren, Diana Karpman, Robin Kahn, Heiko Herwald, Werner Müller-Esterl, Lennart Truedsson, Roland Schmitt |
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Rok vydání: | 2002 |
Předmět: |
Adult
Male Vasculitis Adolescent Immunoblotting Bradykinin Inflammation Enzyme-Linked Immunosorbent Assay Kidney Proinflammatory cytokine Pathogenesis chemistry.chemical_compound medicine Humans Child Skin Kininogen business.industry Kininogens Kidney metabolism Infant General Medicine medicine.disease Immunohistochemistry medicine.anatomical_structure chemistry Child Preschool Immunology Female medicine.symptom business circulatory and respiratory physiology |
Zdroj: | Lancet (London, England). 360(9332) |
ISSN: | 0140-6736 |
Popis: | 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.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.We noted extensive proteolysis of high-molecular-weight kininogen in the plasma of 13 of 17 patients, but in only one of 21 controls (p0.0001). Bradykinin concentrations were higher in the patients' plasma (median 320 ng/L, range1-19680) 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).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. |
Databáze: | OpenAIRE |
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