title: Activation of the ficolin-lectin pathway during attacks of hereditary angioedema.
abstract: 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.
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary; Laboratory of Molecular Medicine, Faculty of Health Sciences, Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. Electronic address: csuka.dorottya@med.semmelweis-univ.hu.
authors.forename: Dorottya
authors.initials: D
authors.lastname: Csuka
authors.affiliation: Laboratory of Molecular Medicine, Faculty of Health Sciences, Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lea
authors.initials: L
authors.lastname: Munthe-Fog
authors.affiliation: Laboratory of Molecular Medicine, Faculty of Health Sciences, Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Estrid
authors.initials: E
authors.lastname: Hein
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Zotter
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Prohászka
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Henriette
authors.initials: H
authors.lastname: Farkas
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Lilian
authors.initials: L
authors.lastname: Varga
authors.affiliation: Laboratory of Molecular Medicine, Faculty of Health Sciences, Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
mesh_terms: D000328:Adult; D054179:Angioedemas, Hereditary / Q000097:blood*; D050718:Complement C1 Inhibitor Protein / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D037102:Lectins / Q000097:blood*; D008297:Male; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000378:metabolism*; D008875:Middle Aged; D015398:Signal Transduction; D055815:Young Adult; D000097604:Ficolins
chemical_list: D050718:Complement C1 Inhibitor Protein; D003181:Complement C4; D006023:Glycoproteins; D037102:Lectins; D050606:Mannose-Binding Protein-Associated Serine Proteases; D000097604:Ficolins; C109662:FCN3 protein, human; C105296:MASP2 protein, human
keywords: C1-inhibitor; Hereditary angioedema; MASPs; edematous attack; ficolins; lectin pathway