The role of ficolins and MASPs in hereditary angioedema due to C1-inhibitor deficiency

Dorottya Csuka; Lea Munthe-Fog; Mikkel-Ole Skjoedt; Andrea Kocsis; Zsuzsanna Zotter; Péter Gál; Lilian Varga; Henriette Farkas; George Füst; Peter Garred

doi:10.1016/j.molimm.2012.12.015

The role of ficolins and MASPs in hereditary angioedema due to C1-inhibitor deficiency

Dorottya Csuka, Lea Munthe-Fog, Mikkel-Ole Skjoedt, Andrea Kocsis, Zsuzsanna Zotter, Péter Gál, Lilian Varga, Henriette Farkas, George Füst, Peter Garred

Department of Clinical Medicine

9 Citations (Scopus)

Abstract

Background and 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.

Original language	English
Journal	Molecular Immunology
Volume	54
Issue number	3-4
Pages (from-to)	271-277
Number of pages	7
ISSN	0161-5890
DOIs	https://doi.org/10.1016/j.molimm.2012.12.015
Publication status	Published - Jul 2013

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10.1016/j.molimm.2012.12.015

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@article{744e1d2d6f69456fa23cf758b0b51e51,

title = "The role of ficolins and MASPs in hereditary angioedema due to C1-inhibitor deficiency",

abstract = "Background and 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.",

author = "Dorottya Csuka and Lea Munthe-Fog and Mikkel-Ole Skjoedt and Andrea Kocsis and Zsuzsanna Zotter and P{\'e}ter G{\'a}l and Lilian Varga and Henriette Farkas and George F{\"u}st and Peter Garred",

year = "2013",

month = jul,

doi = "10.1016/j.molimm.2012.12.015",

language = "English",

volume = "54",

pages = "271--277",

journal = "Molecular Immunology",

issn = "0161-5890",

publisher = "Pergamon Press",

number = "3-4",

}

TY - JOUR

T1 - The role of ficolins and MASPs in hereditary angioedema due to C1-inhibitor deficiency

AU - Csuka, Dorottya

AU - Munthe-Fog, Lea

AU - Skjoedt, Mikkel-Ole

AU - Kocsis, Andrea

AU - Zotter, Zsuzsanna

AU - Gál, Péter

AU - Varga, Lilian

AU - Farkas, Henriette

AU - Füst, George

AU - Garred, Peter

PY - 2013/7

Y1 - 2013/7

N2 - Background and 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.

AB - Background and 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.

U2 - 10.1016/j.molimm.2012.12.015

DO - 10.1016/j.molimm.2012.12.015

M3 - Journal article

C2 - 23318225

SN - 0161-5890

VL - 54

SP - 271

EP - 277

JO - Molecular Immunology

JF - Molecular Immunology

IS - 3-4

ER -

The role of ficolins and MASPs in hereditary angioedema due to C1-inhibitor deficiency

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