PMID- 23940538
OWN - NLM
STAT- MEDLINE
DCOM- 20140305
LR  - 20220330
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 8
DP  - 2013
TI  - Enzymatic assays for the diagnosis of bradykinin-dependent angioedema.
PG  - e70140
LID - 10.1371/journal.pone.0070140 [doi]
LID - e70140
AB  - BACKGROUND: 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. METHODS: 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. RESULTS: 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%). CONCLUSION: The amidase assay represents a 
      diagnostic tool to help physicians in the decision to distinguish between 
      BK-related and -unrelated AE.
FAU - Defendi, Federica
AU  - Defendi F
AD  - Centre de Reference des Angioedemes a Kinines, CREAK, Grenoble, France. 
      FDefendi@chu-grenoble.fr
FAU - Charignon, Delphine
AU  - Charignon D
FAU - Ghannam, Arije
AU  - Ghannam A
FAU - Baroso, Remi
AU  - Baroso R
FAU - Csopaki, Francoise
AU  - Csopaki F
FAU - Allegret-Cadet, Marion
AU  - Allegret-Cadet M
FAU - Ponard, Denise
AU  - Ponard D
FAU - Favier, Bertrand
AU  - Favier B
FAU - Cichon, Sven
AU  - Cichon S
FAU - Nicolie, Brigitte
AU  - Nicolie B
FAU - Fain, Olivier
AU  - Fain O
FAU - Martin, Ludovic
AU  - Martin L
FAU - Drouet, Christian
AU  - Drouet C
CN  - National Reference Centre for Angioedema CREAK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130805
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Complement C1 Inactivator Proteins)
RN  - 0 (Complement C1 Inhibitor Protein)
RN  - 0 (Kinins)
RN  - 0 (SERPING1 protein, human)
RN  - EC 3.5.- (Amidohydrolases)
RN  - EC 3.5.1.4 (amidase)
SB  - IM
EIN - PLoS One. 2014;9(6):e100345
MH  - Amidohydrolases/genetics/metabolism
MH  - Complement C1 Inactivator Proteins/genetics/metabolism
MH  - Complement C1 Inhibitor Protein
MH  - Female
MH  - Hereditary Angioedema Types I and II/*blood/enzymology
MH  - Humans
MH  - Immunoblotting
MH  - Kinins/genetics/metabolism
MH  - Male
MH  - Pregnancy
PMC - PMC3734293
COIS- Competing Interests: OF and LM have read the journal's policy and have the 
      following conflicts: OF and LM received funds from Shire HGT, CSL Behring and 
      ViroPharma. This does not alter the authors' adherence to all the PLOS ONE 
      policies on sharing data and materials. The other authors have declared that no 
      competing interests exist.
FIR - Bergmann, M
IR  - Bergmann M
FIR - Caballero, T
IR  - Caballero T
FIR - Djenouhat, K
IR  - Djenouhat K
FIR - Michel, O
IR  - Michel O
FIR - Vigan, M
IR  - Vigan M
FIR - Pelletier, F
IR  - Pelletier F
FIR - Guez, S
IR  - Guez S
FIR - Ollivier, Y
IR  - Ollivier Y
FIR - Moneret-Vautrin, D-A
IR  - Moneret-Vautrin DA
FIR - Beaudouin, E
IR  - Beaudouin E
FIR - Boccon-Gibod, I
IR  - Boccon-Gibod I
FIR - Bouillet, L
IR  - Bouillet L
FIR - Pagnier, A
IR  - Pagnier A
FIR - Bouvier, M
IR  - Bouvier M
FIR - Coppere, B
IR  - Coppere B
FIR - Maillard, H
IR  - Maillard H
FIR - Launay, D
IR  - Launay D
FIR - Pruvost, I
IR  - Pruvost I
FIR - Grob, J-J
IR  - Grob JJ
FIR - Gayet, S
IR  - Gayet S
FIR - Raison-Peyron, N
IR  - Raison-Peyron N
FIR - Kanny, G
IR  - Kanny G
FIR - Gompel, A
IR  - Gompel A
FIR - Tron, F
IR  - Tron F
FIR - Geny, S
IR  - Geny S
FIR - Vincent, D
IR  - Vincent D
EDAT- 2013/08/14 06:00
MHDA- 2014/03/07 06:00
PMCR- 2013/08/05
CRDT- 2013/08/14 06:00
PHST- 2013/05/14 00:00 [received]
PHST- 2013/06/20 00:00 [accepted]
PHST- 2013/08/14 06:00 [entrez]
PHST- 2013/08/14 06:00 [pubmed]
PHST- 2014/03/07 06:00 [medline]
PHST- 2013/08/05 00:00 [pmc-release]
AID - PONE-D-13-20467 [pii]
AID - 10.1371/journal.pone.0070140 [doi]
PST - epublish
SO  - PLoS One. 2013 Aug 5;8(8):e70140. doi: 10.1371/journal.pone.0070140. Print 2013.