PMID- 32766265
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2296-858X (Print)
IS  - 2296-858X (Electronic)
IS  - 2296-858X (Linking)
VI  - 7
DP  - 2020
TI  - Measurement of Bradykinin Formation and Degradation in Blood Plasma: Relevance 
      for Acquired Angioedema Associated With Angiotensin Converting Enzyme Inhibition 
      and for Hereditary Angioedema Due to Factor XII or Plasminogen Gene Variants.
PG  - 358
LID - 10.3389/fmed.2020.00358 [doi]
LID - 358
AB  - Bradykinin (BK)-mediated angioedema (AE) states are rare acquired or hereditary 
      conditions involving localized edema of the subcutaneous and submucosal tissues. 
      Citrated plasma from healthy volunteers or patients with hereditary angioedema 
      (HAE) with normal level of C1-inhibitor (C1-INH) was used to investigate pathways 
      of BK formation and breakdown relevant to AE physiopathology. The half-life of BK 
      (100 nM) added to normal plasma was 34 s, a value that was increased ~12-fold 
      when the angiotensin converting enzyme (ACE) inhibitor enalaprilat (130 nM) was 
      added (enzyme immunoassay measurements). The BK half-life was similarly increased 
      ~5-fold following 2 daily oral doses of enalapril maleate in healthy volunteers, 
      finding of possible relevance for the most common form of drug-associated AE. We 
      also addressed the kinetics of immunoreactive BK (iBK) formation and decline, 
      spontaneous or under three standardized stimuli: tissue kallikrein (KLK-1), the 
      particulate material Kontact-APTT and tissue plasminogen activator (tPA). 
      Relative to controls, iBK production was rapid (10-20 min) and very intense in 
      response to tPA in plasma of female heterozygotes for variants in gene F12 coding 
      for factor XII (FXII) (p.Thr328Lys, 9 patients; p.Thr328Arg, one). An increased 
      response to Kontact-APTT and an early tPA-induced cleavage of anomalous FXII 
      (immunoblots) were also observed. Biotechnological inhibitors showed that the 
      early response to tPA was dependent on plasmin, FXIIa and plasma kallikrein. 
      Results from post-menopausal and pre-menopausal women with HAE-FXII were 
      indistinguishable. The iBK production profiles in seven patients with the 
      plasminogen p.Lys330Glu variant (HAE-PLG) did not significantly differ from those 
      of controls, except for an unexpected, rapid and lanadelumab-resistant 
      potentiation of KLK-1 effect. This enzyme did not cleave plasminogen or factor 
      XII, suggesting a possible idiosyncratic interaction of the plasminogen 
      pathogenic variant with KLK-1 activity. KLK-1 abounds in salivary glands and 
      human saliva, hypothetically correlating with the clinical presentation of 
      HAE-PLG that includes the swelling of the tongue, lips and contiguous throat 
      tissues. Samples from HAE patients with normal C1-INH levels and F12 gene did not 
      produce excessive iBK in response to stimuli. The ex vivo approach provides 
      physiopathological insight into AE states and supports the heterogeneous 
      physiopathology of HAE with normal C1-INH.
CI  - Copyright (c) 2020 Marceau, Rivard, Gauthier, Binkley, Bonnefoy, Boccon-Gibod, 
      Bouillet, Picard, Levesque, Elfassy, Bachelard, Hebert and Bork.
FAU - Marceau, Francois
AU  - Marceau F
AD  - Axe Microbiologie-Infectiologie et Immunologie, CHU de Quebec-Universite Laval, 
      Quebec, QC, Canada.
FAU - Rivard, Georges E
AU  - Rivard GE
AD  - CHU Sainte-Justine, Universite de Montreal, Montreal, QC, Canada.
FAU - Gauthier, Julie M
AU  - Gauthier JM
AD  - Molecular Diagnostic Laboratory, Division of Medical Genetics, Department of 
      Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, 
      Montreal, QC, Canada.
FAU - Binkley, Karen E
AU  - Binkley KE
AD  - Division of Clinical Immunology and Allergy, Department of Medicine, St. 
      Michael's Hospital, University of Toronto, Toronto, ON, Canada.
FAU - Bonnefoy, Arnaud
AU  - Bonnefoy A
AD  - CHU Sainte-Justine, Universite de Montreal, Montreal, QC, Canada.
FAU - Boccon-Gibod, Isabelle
AU  - Boccon-Gibod I
AD  - National Reference Center for Angioedema (CREAK), Grenoble University Hospital, 
      Grenoble, France.
FAU - Bouillet, Laurence
AU  - Bouillet L
AD  - National Reference Center for Angioedema (CREAK), Grenoble University Hospital, 
      Grenoble, France.
FAU - Picard, Matthieu
AU  - Picard M
AD  - Service d'Immunologie Clinique etl allergie, Departement de Medecine, Hopital 
      Maisonneuve-Rosemont, Montreal, QC, Canada.
FAU - Levesque, Ghislain
AU  - Levesque G
AD  - CLSC Sainte-Rose, Laval, QC, Canada.
FAU - Elfassy, Hannah Laure
AU  - Elfassy HL
AD  - Departement d'Immunologie-Allergie, Hopital du Sacre-Coeur de Montreal, Montreal, 
      QC, Canada.
FAU - Bachelard, Helene
AU  - Bachelard H
AD  - Axe Endocrinologie et Nephrologie, CHU de Quebec-Universite Laval, Quebec, QC, 
      Canada.
FAU - Hebert, Jacques
AU  - Hebert J
AD  - Service d'Allergie, CHU de Quebec-Universite Laval, Quebec, QC, Canada.
FAU - Bork, Konrad
AU  - Bork K
AD  - Department of Dermatology, University Medical Center, Johannes Gutenberg 
      University, Mainz, Germany.
LA  - eng
PT  - Journal Article
DEP - 20200717
PL  - Switzerland
TA  - Front Med (Lausanne)
JT  - Frontiers in medicine
JID - 101648047
PMC - PMC7380097
OTO - NOTNLM
OT  - B2 receptors
OT  - bradykinin
OT  - hereditary angioedema with normal C1 inhibitor level
OT  - kallikreins
OT  - plasmin
OT  - tissue plasminogen activator
EDAT- 2020/08/09 06:00
MHDA- 2020/08/09 06:01
PMCR- 2020/07/17
CRDT- 2020/08/09 06:00
PHST- 2020/04/17 00:00 [received]
PHST- 2020/06/15 00:00 [accepted]
PHST- 2020/08/09 06:00 [entrez]
PHST- 2020/08/09 06:00 [pubmed]
PHST- 2020/08/09 06:01 [medline]
PHST- 2020/07/17 00:00 [pmc-release]
AID - 10.3389/fmed.2020.00358 [doi]
PST - epublish
SO  - Front Med (Lausanne). 2020 Jul 17;7:358. doi: 10.3389/fmed.2020.00358. 
      eCollection 2020.