Contact system activation in patients with HAE and normal C1 inhibitor function.

In addition to hereditary angioedema (HAE) with C1 inhibitor (C1INH) deficiency, a type of HAE with dominant inheritance and normal C1INH function (HAE with normal C1INH) has been described. This relates to contact phase activation with exaggerated kinin formation, and mutations in the coagulation factor XII gene have been identified in some affected families, but the cause of the disease has remained elusive in a majority of families. Several triggering factors are responsible for developing kinin forming system, with participation of endothelium and mast cell component.

Enzymatic assays for the diagnosis of bradykinin-dependent angioedema.

Background: The kinins (primarily bradykinin, BK) represent the mediators responsible for local increase of vascular permeability in hereditary angioedema (HAE), HAE I-II associated with alterations of the SERPING1 gene and HAE with normal C1-Inhibitor function (HAE-nC1INH). Besides C1-Inhibitor function and concentration, no biological assay of kinin metabolism is actually available to help physicians for the diagnosis of angioedema (AE). We describe enzymatic tests on the plasma for diagnosis of BK-dependent AE.

Activation of classical pathway of complement cascade by soluble oligomers of prion.

Mice defective for C1q complement factor show enhanced resistance to peripheral prion inoculation, and previous work demonstrated a direct interaction between C1q and conformationally modified PrP. However, the nature and physiological consequences of this interaction remain uncharacterized. PrP amino acids 141-159 has been identified as a potential C1q binding site; we show, by both surface plasmon resonance (SPR) spectroscopy and ELISA, that C1q and its globular region bind to PrP mutagenized in the region of interest with comparable efficiency to that of wild-type protein.

Characterisation of a new C1 inhibitor mutant in a patient with hepatocellular carcinoma.

A patient developed the first case of hepatocarcinoma associated with hereditary angioedema within the context of a 13-year long prophylactic danazol exposure. We sought to identify the molecular defect and to test the relative contribution to the development of hepatocarcinoma of intracellular accumulation of abnormal C1 inhibitor (C1-INH) protein. The de novo mutation c.