A 29-year-old man with episodic abdominal pain and stress-induced edema of the lips, tongue, and occasionally larynx is likely to have low functional or absolute levels of which of the following proteins?
A. C1 esterase inhibitor
B. C5A (complement cascade)
D. Immunoglobulin (Ig) E
E. T-cell receptor, α chain
The answer is A. (Chap. 372e) Complement activity, which results from the sequential interaction of a large number of plasma and cell membrane proteins, plays an important role in the inflammatory response. The classic pathway of complement activation is initiated by an antibody-antigen interaction. The first complement component (C1, a complex composed of three proteins) binds to immune complexes with activation mediated by C1q. Active C1 then initiates the cleavage and concomitant activation of components C4 and C2. The activated C1 is destroyed by a plasma protease inhibitor termed C1 esterase inhibitor. This molecule also regulates clotting factor XI and kallikrein. Patients with a deficiency of C1 esterase inhibitor may develop angioedema, sometimes leading to death by asphyxia. Attacks may be precipitated by stress or trauma. In addition to low antigenic or functional levels of C1 esterase inhibitor, patients with this autosomal dominant condition may have normal levels of C1 and C3 but low levels of C4 and C2. Danazol therapy produces a striking increase in the level of this important inhibitor and alleviates the symptoms in many patients. An acquired form of angioedema caused by a deficiency of C1 esterase inhibitor has been described in patients with autoimmune or malignant disease.