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High-molecular-weight kininogen cleavage correlates with disease states in the bradykinin-mediated angioedema due to hereditary C1-inhibitor deficiency.
Clin Exp Allergy 2014; 44(12):1503-14CE

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.

Authors+Show Affiliations

Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, Ospedale Luigi Sacco, Milan, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24552232

Citation

Suffritti, C, et al. "High-molecular-weight Kininogen Cleavage Correlates With Disease States in the Bradykinin-mediated Angioedema Due to Hereditary C1-inhibitor Deficiency." Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, vol. 44, no. 12, 2014, pp. 1503-14.
Suffritti C, Zanichelli A, Maggioni L, et al. High-molecular-weight kininogen cleavage correlates with disease states in the bradykinin-mediated angioedema due to hereditary C1-inhibitor deficiency. Clin Exp Allergy. 2014;44(12):1503-14.
Suffritti, C., Zanichelli, A., Maggioni, L., Bonanni, E., Cugno, M., & Cicardi, M. (2014). High-molecular-weight kininogen cleavage correlates with disease states in the bradykinin-mediated angioedema due to hereditary C1-inhibitor deficiency. Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, 44(12), pp. 1503-14. doi:10.1111/cea.12293.
Suffritti C, et al. High-molecular-weight Kininogen Cleavage Correlates With Disease States in the Bradykinin-mediated Angioedema Due to Hereditary C1-inhibitor Deficiency. Clin Exp Allergy. 2014;44(12):1503-14. PubMed PMID: 24552232.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High-molecular-weight kininogen cleavage correlates with disease states in the bradykinin-mediated angioedema due to hereditary C1-inhibitor deficiency. AU - Suffritti,C, AU - Zanichelli,A, AU - Maggioni,L, AU - Bonanni,E, AU - Cugno,M, AU - Cicardi,M, PY - 2013/09/23/received PY - 2014/01/31/revised PY - 2014/02/10/accepted PY - 2014/2/21/entrez PY - 2014/2/21/pubmed PY - 2015/7/24/medline KW - C1-inhibitor deficiency KW - angioedema KW - biomarkers KW - disease severity KW - high-molecular-weight kininogen KW - kallikrein SP - 1503 EP - 14 JF - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology JO - Clin. Exp. Allergy VL - 44 IS - 12 N2 - 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. SN - 1365-2222 UR - https://www.unboundmedicine.com/medline/citation/24552232/High_molecular_weight_kininogen_cleavage_correlates_with_disease_states_in_the_bradykinin_mediated_angioedema_due_to_hereditary_C1_inhibitor_deficiency_ L2 - https://doi.org/10.1111/cea.12293 DB - PRIME DP - Unbound Medicine ER -