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

Csuka, Dorottya and Munthe-Fog, Lea and Skjoedt, Mikkel-Ole and Kocsis, Andrea and Zotter, Zsuzsanna and Gál, Péter and Varga, Lilian and Farkas, Henriette and Füst, György (2013) The role of ficolins and MASPs in hereditary angioedema due to C1-inhibitor deficiency. MOLECULAR IMMUNOLOGY, 54 (3-4). pp. 271-277. ISSN 0161-5890

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Abstract

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.

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