title: BIOBRAD Study: The Search for Biomarkers of Bradykinin-Mediated Angio-Oedema Attacks.
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.
authors.affiliation: Internal Medicine Department, Grenoble University Hospital, Grenoble, France.
authors.forename: Alban
authors.initials: A
authors.lastname: Deroux
authors.forename: Chantal
authors.initials: C
authors.lastname: Dumestre-Perard
authors.forename: Abir
authors.initials: A
authors.lastname: Khalil-Mgharbel
authors.forename: Maxime
authors.initials: M
authors.lastname: Maignan
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boccon-Gibod
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Fevre
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vilgrain
authors.forename: Laurence
authors.initials: L
authors.lastname: Bouillet
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000799:Angioedema / Q000175:diagnosis* / Q000209:etiology*; D015703:Antigens, CD / Q000097:blood; D015415:Biomarkers; D001920:Bradykinin / Q000378:metabolism*; D015820:Cadherins / Q000097:blood; D050718:Complement C1 Inhibitor Protein; D003165:Complement System Proteins; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors; D055815:Young Adult; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D001920:Bradykinin; D015820:Cadherins; D050718:Complement C1 Inhibitor Protein; D003165:Complement System Proteins; D005338:Fibrin Fibrinogen Degradation Products; D000099152:Cadherin 5; C036309:fibrin fragment D