Activation of factor XII and cleavage of high molecular weight kininogen during acute attacks in hereditary and acquired C1-inhibitor deficiencies

Hereditary and acquired C1-inhibitor (C1-INH) deficiencies (hereditary angioedema, HAE and acquired angioedema, AAE) are characterized by episodic increases in vasopermeability due to kinin release. Despite continuously defective C1-INH levels, symptoms only recur occasionally suggesting an episodic generation of pathogenetic factors induced by activation of the protease systems regulated by C1-INH. We evaluated activation of factor XII by measuring plasma levels of FXIIa with a commercial ELISA and cleavage of high molecular weight kininogen by performing SDS PAGE and immunoblotting analysis during 5 attacks in 5 different patients with HAE and during 7 attacks in 3 patients with AAE. The patients were also studied during remission. We confirmed our previous data indicating that during attacks both HAE and AAE patients had very high levels of cleaved HK (p < 0.0001) whereas during remission cleaved HK levels were normal in HAE and significantly increased in AAE (p < 0.0001). Both in HAE and in AAE, plasma levels of FXIIa were normal during remission and significantly increased during acute attacks (p = 0.0126; p = 0.0003). Our data suggest that the activation of a contact system is required to produce clinical symptoms.