Bradykinin-mediated hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH) is often hard to differentiate from mast cell (MC) mediated diseases. MCs can be activated by numerous stimuli, leading to the release of various mediators. Recently, crosstalk between MCs and the complement system has been reported. Clinical observations report a higher prevalence of MC-mediated diseases in the HAE-C1INH population than in the general population. To investigate MC activation in HAE-C1INH. Serum samples from patients during angioedema attack (HAE-A) and during symptom-free period (HAE-SF), as well as from non-angioedema control subjects were examined. Patients and control subjects had no history of allergic disease and normal levels of both nutritional and inhalant specific IgE. Tryptase, chymase, platelet-activating factor (PAF), leukotriene B4 (LTB4), diamine oxidase (DAO), and eosinophil cationic protein (ECP) were measured. Serum level of chymase was higher in both HAE-C1INH groups than in the control group (p = 0.020 in both comparisons), while no difference was found between the HAE-A and HAE-SF groups. DAO and ECP did not differ from the control group, but their levels increased during angioedema attack compared to the asymptomatic state (p = 0.018 and 0.004, respectively). No difference was found in the levels of the other mediators in any comparison. Chymase levels during the symptom-free period were significantly lower in those patients who had more than 3 HAE attack in the three months following sampling than in those who had less than that (p = 0.012). No other mediators showed a difference between these two groups. Significantly higher chymase levels in HAE-C1INH patients raise the possibility of the activation of a specific subset of MCs in HAE-C1INH patients. Elevation of DAO and ECP levels during HAE attacks indicates the involvement of bradykinin-independent pathways in edema formation during HAE attacks.
Horváth et al. (Sat,) studied this question.