Hereditary angioedema is caused by deficiency of which protein, resulting in excess bradykinin and vasodilation?

• A. IgE-mediated
• B. ACE inhibitor effect
• C. C1 deficiency leading to excess bradykinin and vasodilation
• D. C3 deficiency

Answer: (C)

Hereditary angioedema occurs because of deficiency or dysfunction of C1 esterase inhibitor. This protein normally keeps the kallikrein-kinin system in check (and also regulates the classical complement pathway). When C1-INH is deficient, unrestrained kallikrein activity increases production of bradykinin, a potent vasodilator that raises vascular permeability. The resulting bradykinin-driven edema causes swelling without itching or urticaria, and can involve the GI tract or airway. This is distinct from IgE-mediated allergic angioedema (which is histamine-mediated with urticaria) and from C3 deficiency (which leads to infection risk). ACE inhibitors can also raise bradykinin but through a different mechanism, not due to hereditary C1-INH deficiency.