Enzymatic assays for the diagnosis of bradykinin-dependent angioedema.

<h4>Background</h4>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). Besid...

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Autores principales: Federica Defendi, Delphine Charignon, Arije Ghannam, Remi Baroso, Françoise Csopaki, Marion Allegret-Cadet, Denise Ponard, Bertrand Favier, Sven Cichon, Brigitte Nicolie, Olivier Fain, Ludovic Martin, Christian Drouet, National Reference Centre for Angioedema CREAK
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:4088633168934b3f9c8c3f66c332e1c52021-11-18T09:01:25ZEnzymatic assays for the diagnosis of bradykinin-dependent angioedema.1932-620310.1371/journal.pone.0070140https://doaj.org/article/4088633168934b3f9c8c3f66c332e1c52013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23940538/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methods</h4>The plasma amidase assays are performed using the Pro-Phe-Arg-p-nitroanilide peptide substrate to evaluate the spontaneous amidase activity and the proenzyme activation. We analyzed data of 872 patients presenting with BK-dependent AE or BK-unrelated diseases, compared to 303 controls. Anti-high MW kininogen (HK) immunoblot was achieved to confirm HK cleavage in exemplary samples. Reproducibility, repeatability, limit of blank, limit of detection, precision, linearity and receiver operating characteristics (ROC) were used to calculate the diagnostic performance of the assays.<h4>Results</h4>Spontaneous amidase activity was significantly increased in all BK-dependent AE, associated with the acute phase of disease in HAE-nC1INH, but preserved in BK-unrelated disorders. The increase of the amidase activity was associated to HK proteolysis, indicating its relevance to identify kininogenase activity. The oestrogens, known for precipitating AE episodes, were found as triggers of enzymatic activity. Calculations from ROC curves gave the optimum diagnostic cut-off for women (9.3 nmol⋅min(-1)⋅mL(-1), area under curve [AUC] 92.1%, sensitivity 80.0%, and specificity 90.1%) and for men (6.6 nmol·min(-1)⋅mL(-1), AUC 91.0%, sensitivity 87.0% and specificity 81.2%).<h4>Conclusion</h4>The amidase assay represents a diagnostic tool to help physicians in the decision to distinguish between BK-related and -unrelated AE.Federica DefendiDelphine CharignonArije GhannamRemi BarosoFrançoise CsopakiMarion Allegret-CadetDenise PonardBertrand FavierSven CichonBrigitte NicolieOlivier FainLudovic MartinChristian DrouetNational Reference Centre for Angioedema CREAKPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e70140 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Federica Defendi
Delphine Charignon
Arije Ghannam
Remi Baroso
Françoise Csopaki
Marion Allegret-Cadet
Denise Ponard
Bertrand Favier
Sven Cichon
Brigitte Nicolie
Olivier Fain
Ludovic Martin
Christian Drouet
National Reference Centre for Angioedema CREAK
Enzymatic assays for the diagnosis of bradykinin-dependent angioedema.
description <h4>Background</h4>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.<h4>Methods</h4>The plasma amidase assays are performed using the Pro-Phe-Arg-p-nitroanilide peptide substrate to evaluate the spontaneous amidase activity and the proenzyme activation. We analyzed data of 872 patients presenting with BK-dependent AE or BK-unrelated diseases, compared to 303 controls. Anti-high MW kininogen (HK) immunoblot was achieved to confirm HK cleavage in exemplary samples. Reproducibility, repeatability, limit of blank, limit of detection, precision, linearity and receiver operating characteristics (ROC) were used to calculate the diagnostic performance of the assays.<h4>Results</h4>Spontaneous amidase activity was significantly increased in all BK-dependent AE, associated with the acute phase of disease in HAE-nC1INH, but preserved in BK-unrelated disorders. The increase of the amidase activity was associated to HK proteolysis, indicating its relevance to identify kininogenase activity. The oestrogens, known for precipitating AE episodes, were found as triggers of enzymatic activity. Calculations from ROC curves gave the optimum diagnostic cut-off for women (9.3 nmol⋅min(-1)⋅mL(-1), area under curve [AUC] 92.1%, sensitivity 80.0%, and specificity 90.1%) and for men (6.6 nmol·min(-1)⋅mL(-1), AUC 91.0%, sensitivity 87.0% and specificity 81.2%).<h4>Conclusion</h4>The amidase assay represents a diagnostic tool to help physicians in the decision to distinguish between BK-related and -unrelated AE.
format article
author Federica Defendi
Delphine Charignon
Arije Ghannam
Remi Baroso
Françoise Csopaki
Marion Allegret-Cadet
Denise Ponard
Bertrand Favier
Sven Cichon
Brigitte Nicolie
Olivier Fain
Ludovic Martin
Christian Drouet
National Reference Centre for Angioedema CREAK
author_facet Federica Defendi
Delphine Charignon
Arije Ghannam
Remi Baroso
Françoise Csopaki
Marion Allegret-Cadet
Denise Ponard
Bertrand Favier
Sven Cichon
Brigitte Nicolie
Olivier Fain
Ludovic Martin
Christian Drouet
National Reference Centre for Angioedema CREAK
author_sort Federica Defendi
title Enzymatic assays for the diagnosis of bradykinin-dependent angioedema.
title_short Enzymatic assays for the diagnosis of bradykinin-dependent angioedema.
title_full Enzymatic assays for the diagnosis of bradykinin-dependent angioedema.
title_fullStr Enzymatic assays for the diagnosis of bradykinin-dependent angioedema.
title_full_unstemmed Enzymatic assays for the diagnosis of bradykinin-dependent angioedema.
title_sort enzymatic assays for the diagnosis of bradykinin-dependent angioedema.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/4088633168934b3f9c8c3f66c332e1c5
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