Activation of the ficolin-lectin pathway during attacks of hereditary angioedema

作者：Csuka Dorottya^*; Munthe Fog Lea; Hein Estrid; Zotter Zsuzsanna; Prohaszka Zoltan; Farkas Henriette; Varga Lilian; Garred Peter

来源：Journal of Allergy and Clinical Immunology, 2014, 134(6): 1388-+.

DOI：10.1016/j.jaci.2014.05.030

• Hereditary angioedema
• C1-inhibitor
• ficolins
• MASPs
• lectin pathway
• edematous attack

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. %26lt;br%26gt;Objective: Because the role of the ficolin-LP during edematous attacks is still enigmatic, we analyzed its activity during such episodes. %26lt;br%26gt;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. %26lt;br%26gt;Results: Levels of MASP-2 and of the ficolin-3/MASP-2 complex were elevated (P %26lt; .0001 and .033, respectively), whereas that of FCN3-TCC was lower (P %26lt; .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 %26lt; .0001). Both ficolin-3 and MASP-2 levels correlated inversely with the time from the onset of the attack until blood sampling. %26lt;br%26gt;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.

• 出版日期2014-12