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- Title
High-molecular-weight kininogen cleavage correlates with disease states in the bradykinin-mediated angioedema due to hereditary C1-inhibitor deficiency.
- Authors
Suffritti, C.; Zanichelli, A.; Maggioni, L.; Bonanni, E.; Cugno, M.; Cicardi, M.
- Abstract
Background The inherited deficiency of C1-inhibitor (C1- INH), which can be quantitative (type I) or qualitative (type II), is characterized by recurrent attacks of oedema, and it is known as hereditary angioedema due to C1- INH deficiency ( HAE-C1- INH). The frequency of symptoms varies widely among patients and in the same patient during life. Objective To identify laboratory markers of disease severity in HAE-C1- INH patients. Methods We studied 162 patients with differently severe HAE-C1- INH during remission, 31 HAE-C1- INH patients during attacks, and 81 normal controls, evaluating complement parameters, spontaneous plasma kallikrein activity, the capacity of plasma to inhibit exogenous kallikrein activity, and cleavage of high-molecular-weight kininogen ( HK). Sixty-five HAE-C1- INH patients were screened for mutations in the C1- INH gene. Results As expected, plasma C1- INH levels and activity and C4 levels were low in the HAE-C1- INH patients. Spontaneous plasma kallikrein activity in patients in remission was higher than in controls ( P = 0.001) and increased during acute attacks ( P = 0.01), whereas the capacity of inhibiting kallikrein activity was lower in patients in remission than in controls ( P = 0.001) and further reduced during attacks ( P = 0.001). HAE-C1- INH patients in remission had higher levels of cleaved HK than controls ( P = 0.001), and these further increased during acute attacks ( P = 0.001). Cleaved HK levels were higher in highly symptomatic HAE-C1- INH patients than in those with less frequent attacks ( P = 0.001). Thirty-five different mutations in the C1- INH gene were equally distributed in patients with different attack frequencies. Conclusions Measuring plasma levels of cleaved HK may be a sensitive mean of assessing disease severity in HAE-C1- INH patients.
- Subjects
MOLECULAR weights; KININOGENS; BRADYKININ; ANGIONEUROTIC edema; SEVERITY of illness index; DISEASE remission; KALLIKREIN; PHYSIOLOGY
- Publication
Clinical & Experimental Allergy, 2014, Vol 44, Issue 12, p1503
- ISSN
0954-7894
- Publication type
Article
- DOI
10.1111/cea.12293