Plasma levels of C1- inhibitor complexes and cleaved C1- inhibitor in patients with hereditary angioneurotic edema.
C1- inhibitor (C1(-)-Inh) catabolism in plasma of patients with hereditary angioneurotic edema (HANE) was assessed by measuring the complexes formed by C1(-)-Inh with its target proteases (C1-s, Factor XIIa, and kallikrein) and a modified (cleaved) inactive form of C1(-)-Inh (iC1(-)-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 C1(-)-C1(-)-Inh complexes (P less than 0.0001), which in type I inversely correlated with the levels of C1(-)-Inh (P less than 0.001). iC1(-)-Inh was normal in all type-I patients and in type-II patients from three families with increased C1(-)-Inh antigen, whereas iC1(-)-Inh was higher than 20 times the normal values in patients from the remaining two families with C1(-)-Inh antigen in the normal range. None of the subjects had an increase of either Factor XIIa-C1(-)-Inh or kallikrein-C1(-)-Inh complexes. This study shows that the hypercatabolism of C1(-)-Inh in HANE patients at least in part occurs via the formation of complexes with C1- and that genetically determined differences in catabolism of dysfunctional C1(-)-Inh proteins are present in type-II patients.
Cugno
M
M
Cattedra di Clinica Medica Università di Milano, Ospedale S. Paolo, Italy.
Nuijens
J
J
Hack
E
E
Eerenberg
A
A
Frangi
D
D
Agostoni
A
A
Cicardi
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000799:Angioedema / Q000097:blood*; D003174:Complement C1 Inactivator Proteins / Q000032:analysis* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009154:Mutation
D003174:Complement C1 Inactivator Proteins