Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

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

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Collagen VI Contains Multiple Host Defense Peptides with Potent In Vivo Activity

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Multiple Homozygous Variants in the STING-Encoding TMEM173 Gene in HIV Long-Term Nonprogressors

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Antibody-Mediated Neutralization of uPA Proteolytic Function Reduces Disease Progression in Mouse Arthritis Models

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Cyclodextrin Reduces Cholesterol Crystal-Induced Inflammation by Modulating Complement Activation

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Immune regulation by fibroblasts in tissue injury depends on uPARAP-mediated uptake of collectins

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Complement Nomenclature-Deconvoluted

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Evasion of Classical Complement Pathway Activation on Plasmodium falciparum-Infected Erythrocytes Opsonized by PfEMP1-Specific IgG

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

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.

Original languageEnglish
JournalJournal of immunology (Baltimore, Md. : 1950)
Volume195
Issue number8
Pages (from-to)3596-604
Number of pages9
ISSN0022-1767
DOIs
Publication statusPublished - 15 Oct 2015

ID: 45692464