Activation of the ficolin-lectin pathway during attacks of hereditary angioedema.
BACKGROUND
The activation of plasma enzyme systems is insufficiently controlled in hereditary angioedema due to the deficiency of C1-inhibitor (C1-INH) (HAE-C1-INH). Recently, it was suggested that the ficolin-lectin pathway (ficolin-LP) might play a more dominant role than the mannose-binding lectin-lectin pathway in the pathomechanism of HAE-C1-INH.


OBJECTIVE
Because the role of the ficolin-LP during edematous attacks is still enigmatic, we analyzed its activity during such episodes.


METHODS
Thirty-five patients with HAE-C1-INH, who have experienced severe attacks on 106 occasions, were enrolled. We analyzed blood samples drawn during attacks, and obtained 35 samples from the same patients during symptom-free periods. The serum levels of ficolin-2, ficolin-3, MASP-2, ficolin-3/MASP-2 complex, C1-INH, and C4, as well as the extent of ficolin-3-mediated terminal complement complex (FCN3-TCC) deposition, were measured using ELISA-based methods.


RESULTS
Levels of MASP-2 and of the ficolin-3/MASP-2 complex were elevated (P < .0001 and .033, respectively), whereas that of FCN3-TCC was lower (P < .0001) during attacks than during the symptom-free period. During symptom-free periods, FCN3-TCC deposition was significantly related to concentrations of ficolin-3 (R = 0.2778; P = .0022), antigenic C1-INH (R = 0.3152; P = .0006), and C4 (R = 0.5307; P < .0001). Both ficolin-3 and MASP-2 levels correlated inversely with the time from the onset of the attack until blood sampling.


CONCLUSIONS
There is a marked heterogeneity of the pathomechanism and development of hereditary angioedema attacks in different patients. Our results suggest that the activation of the ficolin-LP may deplete the innately low level of C1-INH and thus, it may contribute to the uncontrolled activation of plasma cascade systems, and thereby to edema formation.
['Csuka|Dorottya|D|', 'Munthe-Fog|Lea|L|', 'Hein|Estrid|E|', 'Zotter|Zsuzsanna|Z|', 'Prohászka|Zoltán|Z|', 'Farkas|Henriette|H|', 'Varga|Lilian|L|', 'Garred|Peter|P|']
D000328:Adult D054179:Angioedemas, Hereditary D050718:Complement C1 Inhibitor Protein D003181:Complement C4 D005260:Female D006023:Glycoproteins D006801:Humans D037102:Lectins D008297:Male D050606:Mannose-Binding Protein-Associated Serine Proteases D008875:Middle Aged D015398:Signal Transduction D055815:Young Adult
Hereditary angioedema C1-inhibitor edematous attack MASPs ficolins lectin pathway