Quantification of C1-inhibitor functional activities by immunodiffusion assay in plasma of patients with hereditary angioedema--evidence of a functionally critical level of C1-inhibitor concentration.

The relationship of C1-inhibitor (C1-INH) concentration and apparent functional activity was investigated in 111 plasma samples from 21 patients with the common form of hereditary angioedema (HAE). Functional C1-INH was analyzed by means of a modified version of immunodiffusion assay. Down to a C1-INH level of approximately 0.075 g/l (38% of normal) apparent C1-INH functions were found within the normal range, while below this level functional adequacy of C1-INH could no longer be ascertained. When C4 concentrations, considered to reflect approximately functional C1-INH, were related to C1-INH antigen levels of individual samples, a relationship emerged which was identical to that between C1-INH concentration and apparent function. No attacks of edema could be associated with C1-INH concentrations above 0.075 g/l, while it was possible to associate attacks with concentrations below this level. In experiments where patient plasma and normal plasma were mixed in various ratios or where HAE plasma was replaced by purified C1-INH, an increase in C1-INH antigen to concentrations of 0.06-0.08 g/l was followed by a sharp rise in apparent functions to normal values. The rise of functional C1-INH became moderate when C1-INH antigen further increased. The results supported the idea of a functionally critical level of C1-INH in the common form of HAE.