BIOBRAD Study: The Search for Biomarkers of Bradykinin-Mediated Angio-Oedema Attacks

Int Arch Allergy Immunol. 2016;170(2):108-14. doi: 10.1159/000446959. Epub 2016 Jul 30.

Abstract

Background: The aetiology of angio-oedema (AE) is difficult to determine; however, it is essential in emergency situations when two major contexts may be present: mast cell-mediated AE and bradykinin-mediated AE. Different forms of AE are currently distinguished based on clinical criteria (spontaneous duration of the attack, presence of concomitant or late-appearing superficial urticaria, history of atopy, and others), but specific biomarkers could improve patient management.

Objective: In this prospective study, potential biomarkers have been identified, and their statistical characteristics were examined.

Methods: Samples were taken on day 0 (D0) and D7 for 3 patient groups (n = 11 each): bradykinin-mediated AE [peripheral site of attack, ear, nose, throat (ENT), and abdominal involvement], mast cell-mediated AE, and non-bradykinin-mediated abdominal pain.

Results: Assay of the potential biomarkers revealed no significant differences in C1 inhibitor and C4 levels. In contrast, D-dimer levels peaked during bradykinin-mediated AE attacks (median 2.2 mg/l at D0 vs. 0.52 mg/l at D7; p < 10-3) as well as during mast cell-mediated AE attacks (1.97 vs. 0.65 mg/l; p = 0.04) and were high in bradykinin-mediated AE compared to the control group (0.69 mg/l; p = 0.01). A threshold value of 0.62 mg/l was found to have a negative predictive value of 100% for bradykinin-mediated AE compared to other causes of abdominal pain (group 3). Circulating VE-cadherin levels were also increased during an attack (1,990 at D0 vs. 1,566 ng/ml at D7; p = 0.01), but could not distinguish between bradykinin-mediated and mast cell-mediated AE, like D-dimers.

Conclusions: Exploration of changes in fibrinolysis-related markers (particularly D-dimers) is thus promising for the diagnosis of AE attacks in difficult-to-diagnose abdominal forms, although it was not able to differentiate between bradykinin and mast cell-mediated AE.

Publication types

  • Retracted Publication

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angioedema / diagnosis*
  • Angioedema / etiology*
  • Antigens, CD / blood
  • Biomarkers*
  • Bradykinin / metabolism*
  • Cadherins / blood
  • Complement C1 Inhibitor Protein
  • Complement System Proteins
  • Female
  • Fibrin Fibrinogen Degradation Products
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Time Factors
  • Young Adult

Substances

  • Antigens, CD
  • Biomarkers
  • Cadherins
  • Complement C1 Inhibitor Protein
  • Fibrin Fibrinogen Degradation Products
  • cadherin 5
  • fibrin fragment D
  • Complement System Proteins
  • Bradykinin