Pathogenesis of Hereditary Angioedema: The Role of the Bradykinin-Forming Cascade

Immunol Allergy Clin North Am. 2017 Aug;37(3):513-525. doi: 10.1016/j.iac.2017.04.001.

Abstract

Hereditary angioedema (HAE) is an autosomal-dominant disorder owing to mutations in the C1 inhibitor gene. Type I is characterized by a low C1 inhibitor protein level and diminished functional activity, whereas type II has a normal (or elevated) protein level but diminished function. When functional levels drop beyond 40% of normal, attacks of swelling are likely to occur due to overproduction of bradykinin. Angioedema can be peripheral, abdominal, or laryngeal. The typical duration of episodes is 3 days. Therapies include C1 inhibitor replacement for prophylaxis or acute therapy, whereas inhibition of kallikrein or blockade at the bradykinin receptor level can interrupt acute episodes of swelling.

Keywords: Angioedema; Bradykinin; Factor XII; Kininogen; Prekallikrein.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angioedemas, Hereditary / etiology*
  • Angioedemas, Hereditary / metabolism
  • Bradykinin / metabolism
  • Capillary Permeability
  • Complement Activation / immunology
  • Complement C1 Inhibitor Protein / metabolism
  • Humans
  • Signal Transduction

Substances

  • Complement C1 Inhibitor Protein
  • Bradykinin