Bradykinin driven inflammation

Zonne Liza Michaëla Hofman

Research output: ThesisDoctoral thesis 1 (Research UU / Graduation UU)

Abstract

Bradykinin is an inflammatory peptide that causes a local increase in vascular permeability. We have learned from patients with the disease hereditary angioedema that uncontrolled bradykinin production leads to episodes with swelling of submucosal and subcutaneous tissue. We searched for evidence of bradykinin driven diseases beyond hereditary angioedema as patients with other conditions then HAE may also benefit from therapy developed for this bradykinin driven disorder.
We developed an assay to detect bradykinin release and demonstrated its use as compound diagnostic in drug development for hereditary angioedema. We found evidence for increased bradykinin production in patients with chronic spontaneous urticaria and started a pilot study looking for novel treatment options for patients with idiopathic angioedema. We learned that a novel mutation in Factor XII leads to ongoing bradykinin release in a family with autoinflammatory symptoms. By studying this novel Factor XII mutation, we discovered how FXII zymogen quiescence is regulated.
Original languageEnglish
Awarding Institution
  • University Medical Center (UMC) Utrecht
Supervisors/Advisors
  • Hack, C.E., Primary supervisor
  • Pasterkamp, Gerard, Supervisor
  • Maas, Coen, Co-supervisor
Award date9 Jan 2020
Place of Publication[Utrecht]
Publisher
Print ISBNs978-94-6182-991-7
Publication statusPublished - 9 Jan 2020

Keywords

  • bradykinin
  • angioedema
  • hereditary angioedema
  • Factor XII
  • urticaria
  • allergy

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