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

Cecilie Bo Hansen; Dorottya Csuka; Lea Munthe-Fog; Lilian Varga; Henriette Farkas; Karin Møller Hansen; Claus Koch; Karsten Skjødt; Peter Garred; Mikkel-Ole Skjødt

doi:10.4049/jimmunol.1402838

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

Cecilie Bo Hansen, Dorottya Csuka, Lea Munthe-Fog, Lilian Varga, Henriette Farkas, Karin Møller Hansen, Claus Koch, Karsten Skjødt, Peter Garred, Mikkel-Ole Skjødt

Department of Clinical Medicine

23 Citations (Scopus)

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.

Original language	English
Journal	Journal of immunology (Baltimore, Md. : 1950)
Volume	195
Issue number	8
Pages (from-to)	3596-604
Number of pages	9
ISSN	0022-1767
DOIs	https://doi.org/10.4049/jimmunol.1402838
Publication status	Published - 15 Oct 2015

Keywords

Adult
Angioedemas, Hereditary
Complement C1 Inactivator Proteins
Complement C4
Female
Humans
Male
Mannose-Binding Protein-Associated Serine Proteases
Middle Aged
Multiprotein Complexes
Trauma Severity Indices

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Hansen, C. B., Csuka, D., Munthe-Fog, L., Varga, L., Farkas, H., Hansen, K. M., Koch, C., Skjødt, K., Garred, P., & Skjødt, M-O. (2015). 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. Journal of immunology (Baltimore, Md. : 1950), 195(8), 3596-604. https://doi.org/10.4049/jimmunol.1402838

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. / Hansen, Cecilie Bo; Csuka, Dorottya; Munthe-Fog, Lea et al.

In: Journal of immunology (Baltimore, Md. : 1950), Vol. 195, No. 8, 15.10.2015, p. 3596-604.

Research output: Contribution to journal › Journal article › Research › peer-review

Hansen, CB, Csuka, D, Munthe-Fog, L, Varga, L, Farkas, H, Hansen, KM, Koch, C, Skjødt, K, Garred, P & Skjødt, M-O 2015, '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', Journal of immunology (Baltimore, Md. : 1950), vol. 195, no. 8, pp. 3596-604. https://doi.org/10.4049/jimmunol.1402838

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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.",

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author = "Hansen, {Cecilie Bo} and Dorottya Csuka and Lea Munthe-Fog and Lilian Varga and Henriette Farkas and Hansen, {Karin M{\o}ller} and Claus Koch and Karsten Skj{\o}dt and Peter Garred and Mikkel-Ole Skj{\o}dt",

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doi = "10.4049/jimmunol.1402838",

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T1 - 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

AU - Hansen, Cecilie Bo

AU - Csuka, Dorottya

AU - Munthe-Fog, Lea

AU - Varga, Lilian

AU - Farkas, Henriette

AU - Hansen, Karin Møller

AU - Koch, Claus

AU - Skjødt, Karsten

AU - Garred, Peter

AU - Skjødt, Mikkel-Ole

PY - 2015/10/15

Y1 - 2015/10/15

N2 - 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.

AB - 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.

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KW - Angioedemas, Hereditary

KW - Complement C1 Inactivator Proteins

KW - Complement C4

KW - Female

KW - Humans

KW - Male

KW - Mannose-Binding Protein-Associated Serine Proteases

KW - Middle Aged

KW - Multiprotein Complexes

KW - Trauma Severity Indices

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DO - 10.4049/jimmunol.1402838

M3 - Journal article

C2 - 26371246

SN - 0022-1767

VL - 195

SP - 3596

EP - 3604

JO - Journal of Immunology

JF - Journal of Immunology

IS - 8

ER -

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

Keywords

UN SDGs

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