title: The role of ficolins and MASPs in hereditary angioedema due to C1-inhibitor deficiency.
abstract: 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.
authors: 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary. csukadorka@gmail.com
authors: Dorottya
authors: D
authors: Csuka
authors: Lea
authors: L
authors: Munthe-Fog
authors: Mikkel-Ole
authors: MO
authors: Skjoedt
authors: Andrea
authors: A
authors: Kocsis
authors: Zsuzsanna
authors: Z
authors: Zotter
authors: Péter
authors: P
authors: Gál
authors: Lilian
authors: L
authors: Varga
authors: Henriette
authors: H
authors: Farkas
authors: George
authors: G
authors: Füst
authors: Peter
authors: P
authors: Garred
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000097:blood / Q000378:metabolism; D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000097:blood / Q000378:metabolism; D016022:Case-Control Studies; D050718:Complement C1 Inhibitor Protein / Q000378:metabolism*; D037582:Complement Pathway, Mannose-Binding Lectin; D005260:Female; D006023:Glycoproteins / Q000097:blood / Q000378:metabolism*; D056829:Hereditary Angioedema Types I and II / Q000097:blood / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000097:blood / Q000378:metabolism*; D008297:Male; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000378:metabolism*; D008875:Middle Aged; D055815:Young Adult; D000097604:Ficolins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D050718:Complement C1 Inhibitor Protein; D006023:Glycoproteins; D037102:Lectins; D050606:Mannose-Binding Protein-Associated Serine Proteases; D000097604:Ficolins; C109662:FCN3 protein, human; C428449:MOAP1 protein, human; C084067:MASP1 protein, human; C105296:MASP2 protein, human