New and rapid functional assay for C1 inhibitor in human plasma.
C1 inhibitor (C1-INH) and alpha 2-macroglobulin (alpha 2M) account for over 90% of the inactivation of purified plasma kallikrein by normal human plasma. The rate of kallikrein inactivation is also dependent on the presence of high molecular weight kininogen (HMWK), which forms a reversible complex with kallikrein protecting the active site of the enzyme against inhibitors. By selectively inactivating alpha 2M with methylamine, and eliminating the protective effect of HMWK by dilution, the inactivation of kallikrein by plasma became almost exclusively dependent on C1-INH. Functional C1 inhibitor was assessed by measuring the pseudo-first-order rate constant for the inactivation of kallikrein by diluted methylamine-treated plasma in 29 individuals, including 11 controls, 11 oral contraceptive users, 5 patients with classical hereditary angioedema (HAE), and 2 patients with variant HAE. Over a wide range of concentrations, an excellent correlation (r = 0.90) was observed between functional and antigenic C1-INH among controls, oral contraceptive users, and patients with classical HAE. This new functional assay for C1-INH can be performed in less than 3 hr with commercially available reagents. Therefore, this assay will be helpful for the diagnosis and management of conditions associated with the deficiency of C1-INH, such as HAE.
D000799:Angioedema / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D000941:Antigens / Q000032:analysis; D003174:Complement C1 Inactivator Proteins / Q000032:analysis* / Q000172:deficiency / Q000276:immunology; D005260:Female; D006801:Humans; D007610:Kallikreins / Q000097:blood; D007700:Kinetics; D007704:Kininogens / Q000097:blood; D008297:Male; D008744:Methylamines / Q000494:pharmacology; D008970:Molecular Weight; D000511:alpha-Macroglobulins / Q000172:deficiency
D000941:Antigens; D003174:Complement C1 Inactivator Proteins; D007704:Kininogens; D008744:Methylamines; D000511:alpha-Macroglobulins; D007610:Kallikreins