The role of ficolins and MASPs in hereditary angioedema due to C1-inhibitor deficiency.

BACKGROUND AND OBJECTIVE: Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) causes disturbances in the complement system. However, the influence of HAE-C1-INH on the lectin pathway of complement is unresolved. Thus, we studied the main initiator molecules, enzymes and regulators in the lectin pathway in patients with HAE-C1-INH.

METHODS: The serum concentrations of ficolin-2, ficolin-3, MBL, MASP-2, MASP-3, and MAP-1 were measured during symptom-free periods in 91 patients with HAE-C1-INH, and in 100 healthy controls using sandwich ELISAs.

RESULTS: Compared with controls, the levels of ficolin-2 (p<0.0001) and MASP-2 (p=0.0238) were reduced, while the levels of MBL and MASP-3 were elevated (p=0.0028 and p<0.0001, respectively) in HAE-C1-INH patients. Ficolin-3 and MAP-1 levels did not differ significantly between the two groups. Ficolin-2 correlated with MASP-3 in patients (r=0.3443, p=0.0008), while these parameters showed an opposite relationship in controls (r=-0.4625, p<0.0001). In the patients, ficolin-3 correlated with MASP-2 (r=0.3698, p=0.001). Ficolin-2, -3, and MAP-1 correlated negatively with the annual requirement of plasma derived C1-INH concentrate (r=-0.2863, p=0.0059; r=-0.2654, p=0.0110 and r=-0.2501, p=0.0168, respectively). Ficolin-3 showed a negative correlation with the annual number of attacks (r=-0.2478, p=0.0179).

CONCLUSIONS: We found significant differences between patients and controls in the levels of some of the molecules belonging to the lectin complement pathway. Low concentrations of particularly ficolin-2 and -3 were inversely correlated with the severity of HAE-C1-INH, while this was not observed for MBL. This suggests a previously unrecognized involvement of the ficolin-dependent lectin complement pathway in the pathophysiology of HAE-C1-INH.