Behavior in vivo of normal and dysfunctional Cl̄ inhibitor in normal subjects and patients with hereditary angioneurotic edema

Abstract

The metabolism of normal Cl̄ inhibitor and two dysfunctional Cl̄ inhibitors (Ta and Wel) was studied in 10 normal subjects and 8 patients with hereditary angioneurotic edema (HANE), 4 with low antigen concentration (type 1) and 4 with dysfunctional protein (type 2). The fractional catabolic rate of the normal Cl̄ inhibitor in normal subjects was 0.025 of the plasma pool/hour, whereas in HANE subjects it was significantly elevated at 0.035 of the plasma pool/hour. The synthesis of normal Cl̄ inhibitor was decreased in patients with type 1 HANE (0.087 mg/kg per h compared with 0.218 mg/kg per h). The fractional catabolic rate of dysfunctional protein Wel was similar to normal and showed a slightly accelerated catabolism in patients with HANE, whereas the dysfunctional protein Ta had a strikingly decreased fractional catabolic rate in normals and subjects with HANE. The present study is compatible with reduced Cl̄ inhibitor synthesis in patients with type 1 HANE consistent with a single functional Cl̄ inhibitor gene. The lower than anticipated levels of Cl̄ inhibitor in HANE type 1 appears to result from (a) the single functional gene and (b) increased catabolism of the protein, perhaps related to activation of Cl̄ or other proteases.