Action of Complement in Hereditary Angioneurotic Edema: The Role of C′1-Esterase *

Inherited deficiency of the third component of human complement (C′3)

“…By contrast, the deficiency of C'1 esterase inhibitor activity in patients with hereditary angioneurotic edema, whether associated with quantitatively or qualitatively deficient protein (1)(2)(3), is transmitted as an autosomal dominant trait.…”

“…It is now clear that such low activity may be associated either with a deficiency of the protein bearing this activity or with normal concentrations of presumably aberrant protein. This has been well illustrated in hereditary angioneurotic edema where all affected individuals lack demonstrable C'1 esterase inhibitor activity (1,2). In most affected kindred, individuals with the disease have very low serum concentrations of the inhibitor by immunochemical assay, whereas in other families affected individuals have normal concentrations in the serum of a functionless protein, antigenically indistinguishable from active C'1 esterase inhibitor (3).…”

Type I C1 inhibitor deficiency with a small messenger RNA resulting from deletion of one exon.

“…Hereditary angioneurotic edema (HANE)l is a genetic disease resulting from heterozygous deficiency of the inhibitor of the first component ofcomplement (Cl INH) (1,2). The disease is therefore inherited as an autosomal dominant trait, and is characterized clinically by recurrent, acute, local edema of the skin or mucosa (3,4).…”

“…In type I, a normal Cl INH protein is present in plasma at reduced levels of from 5 to 30% of normal. Type II is characterized by normal-to-ele- 1. Abbreviations used in this paper: C1 INH, C1 inhibitor; HANE, hereditary angioneurotic edema; PCR, polymerase chain reaction; RFLP, restriction fragment length polymorphism.…”

“…Previous findings, including in vitro synthesis of Cl INH by cultured monocytes (8), metabolic turnover of Cl INH (9), and analysis of restriction fragment length polymorphism (RFLP) (10) were consistent with the hypothesis that patients are heterozygous for the defect. Genetic analysis of HANE indicates that the molecular genetic defects responsible for Cl INH deficiency are heterogeneous, as are those responsible for many other genetic diseases (1 [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Analysis of mutant proteins from type II HANE patients provided the first evidence for genetic heterogeneity: the proteins from different families differ in electrophoretic mobility, size, and function (6,15,16).…”