Marcatori di severità di malattia nei soggetti con angioedema da carenza C1 inibitore.

Markers of disease severity in angioedema due to C1 inhibitor deficiency Background Hereditary angioedema (HAE) is characterized by recurrent attacks of edema affecting skin, gastrointestinal tract, and larynx. HAE results from an inherited deficiency (type I) or dysfunction (type II) of C1 inhibitor (C1-INH). C1-INH has a broad spectrum of activities inhibiting complement, contact system, coagulation and fibrinolysis. During acute attacks, unregulated active kallikrein cleaves high-molecular weight kininogen (HK) releasing bradykinin, the mediator of the increased vascular permeability. Despite the deficiency of C1-INH is constant in HAE, angioedema symptoms are intermittent and their frequency is highly variable among patients and in the same individual during life. Objective To identify predictive markers of disease severity in HAE for therapeutic approach. Methods We measured cleaved HK and complement parameters (functional C1-INH, antigenic C1-INH, C4, C1q) in 123 HAE patients during remission. Between patients without therapy, 23 had high frequency of angioedema attacks (>12 attacks/year), 18 had intermediate frequency (3-12 attacks/year) and 22 had low frequency (<3 attacks/year). Ten HAE patients were studied during 16 different acute attacks. As control group we studied 61 healthy subjects. Results Cleaved HK in HAE patients during remission (mean 44%±9) was significantly higher (P=0.0001) than in healthy controls (mean 35%±5) and further increased during acute attacks (58%±7) (P=0.0001). Cleaved HK was significantly increased during remission in patients with >12 attacks/year compared to those with <3 attacks/year and also to those with 3-12 attacks/year (p=0.04). C4 antigen levels were significantly higher in patients with sporadic symptoms than in patients with high frequency of attacks (>12 attacks/year). Conclusions Our findings demonstrate that the measurement of cleaved HK can help identifying patients at risk for angioedema symptoms. Evaluation of the cleavage of HK may represent a sensitive tool for monitoring HAE patients.