High-molecular-weight kininogen cleavage correlates with disease states in the bradykinin-mediated angioedema due to hereditary C1-inhibitor deficiency

C. Suffritti, A. Zanichelli, L. Maggioni, E. Bonanni, M. Cugno, M. Cicardi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1503-1514
Number of pages12
JournalClinical and Experimental Allergy
Volume44
Issue number12
DOIs
Publication statusPublished - Dec 1 2014

Keywords

  • Angioedema
  • Biomarkers
  • C1-inhibitor deficiency
  • Disease severity
  • High-molecular-weight kininogen
  • Kallikrein

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Medicine(all)

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