Background
The pathophysiology of the underlying paroxysmal permeability disturbances in angioedema (AE) is not well understood.
Methods
To identify clinical and laboratory parameters specific for a certain AE subtype, 40 AE patients were prospectively enrolled: 15 hereditary (HAE), 13 ACE‐inhibitor induced (ACE‐AE), and 12 mast cell‐mediated without wheals in chronic spontaneous urticaria (CSU‐AE). Ten healthy subjects served as controls. Serum levels of markers indicating activation of the ficolin‐lectin pathway, of endothelial cells, or those indicating impairment of vascular integrity or inflammation were assessed by enzyme‐linked immunosorbent assay.
Results
New routine clinical diagnostic criteria could not be identified, not even for distinguishing bradykinin‐mediated (BK‐) AE (ie, HAE and ACE‐AE) from mast cell‐/histamine‐mediated CSU‐AE. However, FAP‐α and tPA were significantly increased in all AE compared to controls. In HAE, FAP‐ α, tPA, uPAR, pentraxin‐3, Tie‐2, sE‐selectin, and VE‐cadherin were significantly increased compared to controls. In HAE compared to CSU‐AE and ACE‐AE, sE‐Selectin, Tie‐2, and VE‐Cadherin were significantly increased, whereas for Ang‐2 the difference was significant compared to CSU‐AE only. Tie‐2 correlated strongly negatively with C4, C1‐INH activity, and C1‐INH function.
Conclusions
This study is the first to compare HAE, ACE‐AE, and CSU‐AE. Although significance is limited by small sample size, Tie‐2 was identified as a new promising biomarker candidate for HAE. FAP‐ α and tPA might serve as a marker for AE in general, whereas sE‐selectin and Ang‐2 were increased in BK‐AE only. Our results add information to the role of endothelial dysfunction and serine proteases in different AE subtypes.
