Current update on cellular and molecular mechanisms of hereditary angioedema.
OBJECTIVE
To provide an update on the molecular mechanisms of hereditary angioedema (HAE).


METHODS
MEDLINE and PubMed databases were searched to identify pertinent articles using the following key terms: hereditary angioedema, angioedema, C1 inhibitor, bradykinin, contact system, factor XII, mechanism, pathophysiology, severity, permeability, and estrogen.


METHODS
Articles were selected based on their relevance to the subject matter.


RESULTS
Although the biochemical basis of "classic" HAE is known to result from C1 esterase inhibitor (C1INH) deficiency, a new form, HAE with normal C1INH, has been identified. HAE types I and II are caused by mutations in the SERPING1 gene that result in decreased plasma levels of functional C1INH. In HAE with normal C1INH, mutations in the F12 gene have been identified in a subset of individuals, but the genetic defect remains unknown in most patients. The primary mediator of swelling in HAE is bradykinin, a product of the plasma contact system that increases vascular permeability. HAE disease severity is highly variable and may be influenced by polymorphisms in other genes and other factors, such as hormones, trauma, stress, and infection.


CONCLUSIONS
Hereditary angioedema is a heterogeneous disorder with a complex pathophysiology. Implicated genes include SERPING1 and FXII in patients with HAE from C1INH deficiency and HAE with normal C1INH levels, respectively. Disease severity is highly variable.
Department of Medicine, University of California-San Diego, La Jolla, California.
Hannah H
HH
Walford
Department of Medicine, University of California-San Diego, La Jolla, California; San Diego Veteran's Administration Healthcare, San Diego, California. Electronic address: bzuraw@ucsd.edu.
Bruce L
BL
Zuraw
D054179:Angioedemas, Hereditary / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001920:Bradykinin / Q000276:immunology; D002648:Child; D003174:Complement C1 Inactivator Proteins / Q000235:genetics / Q000276:immunology; D050718:Complement C1 Inhibitor Protein; D004967:Estrogens / Q000378:metabolism; D005174:Factor XII / Q000235:genetics; D005175:Factor XII Deficiency / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male
D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D004967:Estrogens; C469952:SERPING1 protein, human; D005174:Factor XII; D001920:Bradykinin