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Kininogen Cleavage Assay: Diagnostic Assistance for Kinin-Mediated Angioedema Conditions

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Listed:
  • Rémi Baroso
  • Pauline Sellier
  • Federica Defendi
  • Delphine Charignon
  • Arije Ghannam
  • Mohammed Habib
  • Christian Drouet
  • Bertrand Favier

Abstract

Background: Angioedema without wheals (AE) is a symptom characterised by localised episodes of oedema presumably caused by kinin release from kininogen cleavage. It can result from a hereditary deficiency in C1 Inhibitor (C1Inh), but it can present with normal level of C1Inh. These forms are typically difficult to diagnose although enhanced kinin production is suspected or demonstrated in some cases. Objectives: We wanted to investigate bradykinin overproduction in all AE condition with normal C1Inh, excluding cases with enhanced kinin catabolism, and to propose this parameter as a disease biomarker. Methods: We retrospectively investigated high molecular weight kininogen (HK) cleavage pattern, using gel electrophoresis and immunorevelation. Plasma samples were drawn using the same standardised procedure from blood donors or AE patients with normal C1Inh conditions, normal kinin catabolism, and without prophylaxis. Results: Circulating native HK plasma concentrations were similar in the healthy men (interquartile range: 98–175μg/mL, n = 51) and in healthy women (90–176μg/mL, n = 74), while HK cleavage was lower (p 14.4% HK cleavage for men; 33.0% HK cleavage for women, with >98% specificity achieved for all parameters. In plasma from patients undergoing recovery two months after oestrogen/progestin combination withdrawal (n = 13) or two weeks after AE attack (n = 2), HK cleavage was not fully restored, suggesting its use as a post-attack assay. Conclusion: As a diagnostic tool, HK cleavage can offer physicians supportive arguments for kinin production in suspected AE cases and improve patient follow-up in clinical trials or prophylactic management.

Suggested Citation

  • Rémi Baroso & Pauline Sellier & Federica Defendi & Delphine Charignon & Arije Ghannam & Mohammed Habib & Christian Drouet & Bertrand Favier, 2016. "Kininogen Cleavage Assay: Diagnostic Assistance for Kinin-Mediated Angioedema Conditions," PLOS ONE, Public Library of Science, vol. 11(9), pages 1-16, September.
    • Handle: RePEc:plo:pone00:0163958
    DOI: 10.1371/journal.pone.0163958
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