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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.
AuthorsCecilie Bo Hansen, Dorottya Csuka, Lea Munthe-Fog, Lilian Varga, Henriette Farkas, Karin Møller Hansen, Claus Koch, Karsten Skjødt, Peter Garred, Mikkel-Ole Skjoedt
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 195 Issue 8 Pg. 3596-604 (Oct 15 2015) ISSN: 1550-6606 [Electronic] United States
PMID26371246 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 by The American Association of Immunologists, Inc.
Chemical References
  • Complement C1 Inactivator Proteins
  • Complement C1 Inhibitor Protein
  • Complement C4
  • Multiprotein Complexes
  • SERPING1 protein, human
  • MASP1 protein, human
  • Mannose-Binding Protein-Associated Serine Proteases
Topics
  • Adult
  • Angioedemas, Hereditary (blood, immunology, pathology)
  • Complement C1 Inactivator Proteins (immunology, metabolism)
  • Complement C1 Inhibitor Protein
  • Complement C4 (immunology, metabolism)
  • Female
  • Humans
  • Male
  • Mannose-Binding Protein-Associated Serine Proteases (immunology, metabolism)
  • Middle Aged
  • Multiprotein Complexes (blood, immunology)
  • Trauma Severity Indices

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