Effects of C1-inhibitor deficiency and bradykinin excess on human biology
Hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is a rare autosomal dominant disease with an uncertain prevalence estimated to be 1: 50 000 and is caused by mutation in the SERPING1 gene. It is characterized by non-pruritic, episodic and self-limiting swellings in skin and submucosal tissue without urticaria. Laryngeal edema can be fatal.
C1-INH inhibits the enzymes C1r, C1s, mannose-associated serine protease (MASP) -1 and -2 in the complement system, activated factor XII, clotting factor XI, plasma kallikrein, plasmin and other factors. Deficiency of C1-INH results in an uncontrolled activation of these cascade systems. Uncontrolled activation of kallikrein increases the cleavage of high molecular weight kininogen and releases bradykinin. Bradykinin is responsible for plasma leakage and edema. Histamine and mast cells are not directly involved, and C1-INH-HAE-patients do not respond to treatment with steroids and/or antihistamines. HAE-patients may produce bradykinin ten times normal levels during remission and hundred times normal levels under attacks of edema. Bradykinin is a known mediator of pain, but the physiology of pain has not been studied in HAE-patients until now. Bradykinin is also a potent chemoattractant and a mediator of inflammation. The behavior of HAE-plasma and whole blood in response to exogenously added triggers and inhibitors of inflammation has not been studied in sufficient detail.
A deeper knowledge of C1-INH-HAE is vital since attacks are painful and thrombosis and inflammation could influence symptoms.
- Samarbeid med Oslo universitetssykehus
- Samarbeidsinstitusjon er forskningsansvarlig
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