Acquired C1 esterase inhibitor deficiency secondary to malignant disease is also manifested by depressed C1 esterase inhibitor and C4, but decreased C1q levels distinguish it from hereditary angioedema.
The subjects belonged to two Finnish families representing the more common form of HANE which is recognized by the immunochemically observed decrease of the inhibitor (C1-INH) blocking the esterase activity of the first complement component.
Remissions induced in hereditary angioneurotic edema with an attenuated androgen (danazol): correlation between concentrations of C1-inhibitor and the forth and second components of complement.
Specific functional and immunologic assay of plasma plasminogen in hereditary angioedema, in hereditary angioedema treated with tranexamic acid, and in normal subjects.
Other genetic markers studied were generally noninformative, although evidence was obtained against close linkage of the loci for HAE and ABO and HAE and transferrins.
We have examined the response to danazol therapy of patients with the variant HAE phenotypes possessing the abnormal protein in an effort to determine if these patients possess a normal structural C1 inhibitor allele.
Four patients, with a clinical history of hereditary angioedema and a demonstrated depression of the serum inhibitor of the first component of complement (C1 INH) and the fourth component of complement (C4), were entered into a study to determine the minimum effective dose of this agent.
Members of two Australian families with type A Hereditary Angioedema (HAE), having affected individuals in three generations, were typed for a large number of genetic marker systems in a search for close linkage with the locus controlling C1 inhibitor (C1 inh).
treatment of hereditary angio-oedema by low dose attenuated androgens: disassociation of clinical response from levels of C1 esterase inhibitor and C4.
From these studies of purified C1INH proteins we concluded that HAE associated with dysfunctional C1INH is due to a defect at the structural locus for one C1INH gene and that both the dysfunctional C1INH gene and the normal C1INH gene products are present in the plasma of the affected subject.
In spite of the fact that patients suffering from HAE severely lack C1 INH, neither the intrinsic coagulation nor the fibrinolytic systems are impaired.
The lower than anticipated levels of C1 inhibitor in HANE type 1 appears to result from (a) the single functional gene and (b) increased catabolism of the protein, perhaps related to activation of C1 or other proteases.
Treatment of patients with hereditary angioedema with stanozolol or danocrine increased their serum C1 inhibitor concentrations and normalized the immunodiffusion assay for C1 inhibitor function.
We therefore propose that bradykinin alone, or in combination with other factors heretofore unrecognized, might be responsible for the swelling that is characteristic of hereditary angioedema.
This abnormality is thought to be responsible for the generation of a kininlike peptide in HAE plasma that is derived from the second component of complement (C2).
Incubation of HAE sera with highly purified Hageman factor fragment (5 micrograms/ml), or aggregated IgG (2 mg/ml) was found to accelerate the rate of decay when compared to untreated samples while sera from patients under treatment with Danazol or Stanozolol failed to autoactive.
In 13 HANE-I patients there were significantly increased levels of the coagulation factors XII, XI, V, of plasminogen and of alpha 2-antiplasmin, while the factors IX and VII were decreased.