title: The Levels of the Lectin Pathway Serine Protease MASP-1 and Its Complex Formation with C1 Inhibitor Are Linked to the Severity of Hereditary Angioedema.
abstract: C1 inhibitor (C1-INH) is known to form complexes with the lectin complement pathway serine proteases MASP-1 and MASP-2. Deficiency of C1-INH is associated with hereditary angioedema (HAE), an autosomal inherited disease characterized by swelling attacks caused by elevated levels of bradykinin. MASP-1 was shown to cleave high m.w. kininogen into bradykinin; therefore, we hypothesized that MASP-1 levels and the quantity of MASP-1/C1-INH complexes might be associated with different paraclinical and clinical outcomes of HAE. We measured MASP-1 serum concentrations and endogenous MASP-1/C1-INH complex levels in 128 HAE patients and 100 controls. Relatively high levels of pre-existing MASP-1/C1-INH complexes were observed in normal serum, and we found that both the serum levels of MASP-1 and the complex formation between MASP-1 and C1-INH were significantly reduced in HAE patients compared with matched controls (p < 0.0001). The level of MASP-1 and MASP-1/C1-INH complexes in HE patients correlated with the level of C1-INH (p = 0.0009 and p = 0.0047, respectively), the level of C4 (p = 0.0084 and p < 0.0001, respectively), and the number of attacks in the year of blood sampling (p = 0.0075 and p = 0.0058, respectively). In conclusion, we show that MASP-1/C1-INH complexes circulate in normal human blood. The levels of MASP-1 and MASP-1/C1-INH complexes are reduced in HAE patients compared with controls. Both MASP-1 and MASP-1/C1-INH complexes are related to the degree of complement C4 consumption, as well as the severity of disease. These results suggest that MASP-1 may exert a previously unrecognized role in the pathophysiology of HAE.
authors.affiliation: Laboratory of Molecular Medicine, Department of Clinical Immunology, Faculty of Health and Medical Sciences, University Hospital of Copenhagen, 2200 Copenhagen, Denmark;
authors.forename: Cecilie Bo
authors.initials: CB
authors.lastname: Hansen
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, Budapest 1085, Hungary; and.
authors.forename: Dorottya
authors.initials: D
authors.lastname: Csuka
authors.affiliation: Laboratory of Molecular Medicine, Department of Clinical Immunology, Faculty of Health and Medical Sciences, University Hospital of Copenhagen, 2200 Copenhagen, Denmark;
authors.forename: Lea
authors.initials: L
authors.lastname: Munthe-Fog
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, Budapest 1085, Hungary; and.
authors.forename: Lilian
authors.initials: L
authors.lastname: Varga
authors.affiliation: 3rd Department of Internal Medicine, Semmelweis University, Budapest 1085, Hungary; and.
authors.forename: Henriette
authors.initials: H
authors.lastname: Farkas
authors.affiliation: Laboratory of Molecular Medicine, Department of Clinical Immunology, Faculty of Health and Medical Sciences, University Hospital of Copenhagen, 2200 Copenhagen, Denmark;
authors.forename: Karin Møller
authors.initials: KM
authors.lastname: Hansen
authors.affiliation: Department of Cancer and Inflammation, University of Southern Denmark, 5000 Odense, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Koch
authors.affiliation: Department of Cancer and Inflammation, University of Southern Denmark, 5000 Odense, Denmark.
authors.forename: Karsten
authors.initials: K
authors.lastname: Skjødt
authors.affiliation: Laboratory of Molecular Medicine, Department of Clinical Immunology, Faculty of Health and Medical Sciences, University Hospital of Copenhagen, 2200 Copenhagen, Denmark;
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
authors.affiliation: Laboratory of Molecular Medicine, Department of Clinical Immunology, Faculty of Health and Medical Sciences, University Hospital of Copenhagen, 2200 Copenhagen, Denmark; moskjoedt@gmail.com.
authors.forename: Mikkel-Ole
authors.initials: MO
authors.lastname: Skjoedt
mesh_terms: D000328:Adult; D054179:Angioedemas, Hereditary / Q000097:blood / Q000276:immunology* / Q000473:pathology; D003174:Complement C1 Inactivator Proteins / Q000276:immunology* / Q000378:metabolism; D050718:Complement C1 Inhibitor Protein; D003181:Complement C4 / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D046912:Multiprotein Complexes / Q000097:blood / Q000276:immunology*; D015599:Trauma Severity Indices
chemical_list: D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D003181:Complement C4; D046912:Multiprotein Complexes; C469952:SERPING1 protein, human; C084067:MASP1 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases