PLASMA-LEVELS OF C1 INHIBITOR COMPLEXES AND CLEAVED C1 INHIBITOR IN PATIENTS WITH HEREDITARY ANGIONEUROTIC-EDEMA

C1̄ inhibitor (C1̄-Inh) catabolism in plasma of patients with hereditary angioneurotic edema (HANE) was assessed by measuring the complexes formed by C1̄-Inh with its target proteases (C1̄s, Factor XIIa, and kallikrein) and a modified (cleaved) inactive form of C1̄-Inh (iC1̄-Inh). This study was performed in plasma from 18 healthy subjects and 30 patients with HANE in remission: 20 with low antigen concentration (type I) and 10 (from 5 different kindreds) with dysfunctional protein (type II). Both type-I and type-II patients had increased C1̄-C1̄-Inh complexes (P < 0.0001), which in type I inversely correlated with the levels of C1̄-Inh (P < 0.001). iC1̄-Inh was normal in all type-I patients and in type-II patients from three families with increased C1̄-Inh antigen, whereas iC1̄-Inh was higher than 20 times the normal values in patients from the remaining two families with C1̄-Inh antigen in the normal range. None of the subjects had an increase of either Factor XIIa-C1̄-Inh or kallikrein-C1̄-Inh complexes. This study shows that the hypercatabolism of C1̄-Inh in HANE patients at least in part occurs via the formation of complexes with C1̄ and that genetically determined differences in catabolism of dysfunctional C1̄-Inh proteins are present in type-II patients.