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Activation of the ficolin-lectin pathway during attacks of hereditary angioedema

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Activation of the ficolin-lectin pathway during attacks of hereditary angioedema. / Csuka, Dorottya; Munthe-Fog, Lea; Hein, Estrid; Zotter, Zsuzsanna; Prohászka, Zoltán; Farkas, Henriette; Varga, Lilian; Garred, Peter.

I: The Journal of allergy and clinical immunology, Bind 134, Nr. 6, 12.2014, s. 1388–1393.e1.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Csuka, D, Munthe-Fog, L, Hein, E, Zotter, Z, Prohászka, Z, Farkas, H, Varga, L & Garred, P 2014, 'Activation of the ficolin-lectin pathway during attacks of hereditary angioedema', The Journal of allergy and clinical immunology, bind 134, nr. 6, s. 1388–1393.e1. https://doi.org/10.1016/j.jaci.2014.05.030

APA

Csuka, D., Munthe-Fog, L., Hein, E., Zotter, Z., Prohászka, Z., Farkas, H., Varga, L., & Garred, P. (2014). Activation of the ficolin-lectin pathway during attacks of hereditary angioedema. The Journal of allergy and clinical immunology, 134(6), 1388–1393.e1. https://doi.org/10.1016/j.jaci.2014.05.030

Vancouver

Csuka D, Munthe-Fog L, Hein E, Zotter Z, Prohászka Z, Farkas H o.a. Activation of the ficolin-lectin pathway during attacks of hereditary angioedema. The Journal of allergy and clinical immunology. 2014 dec;134(6):1388–1393.e1. https://doi.org/10.1016/j.jaci.2014.05.030

Author

Csuka, Dorottya ; Munthe-Fog, Lea ; Hein, Estrid ; Zotter, Zsuzsanna ; Prohászka, Zoltán ; Farkas, Henriette ; Varga, Lilian ; Garred, Peter. / Activation of the ficolin-lectin pathway during attacks of hereditary angioedema. I: The Journal of allergy and clinical immunology. 2014 ; Bind 134, Nr. 6. s. 1388–1393.e1.

Bibtex

@article{f7523c19a8ee475398e79bd4368f0b9b,
title = "Activation of the ficolin-lectin pathway during attacks of hereditary angioedema",
abstract = "BACKGROUND: The activation of plasma enzyme systems is insufficiently controlled in hereditary angioedema due to the deficiency of C1-inhibitor (C1-INH) (HAE-C1-INH). Recently, it was suggested that the ficolin-lectin pathway (ficolin-LP) might play a more dominant role than the mannose-binding lectin-lectin pathway in the pathomechanism of HAE-C1-INH.OBJECTIVE: Because the role of the ficolin-LP during edematous attacks is still enigmatic, we analyzed its activity during such episodes.METHODS: Thirty-five patients with HAE-C1-INH, who have experienced severe attacks on 106 occasions, were enrolled. We analyzed blood samples drawn during attacks, and obtained 35 samples from the same patients during symptom-free periods. The serum levels of ficolin-2, ficolin-3, MASP-2, ficolin-3/MASP-2 complex, C1-INH, and C4, as well as the extent of ficolin-3-mediated terminal complement complex (FCN3-TCC) deposition, were measured using ELISA-based methods.RESULTS: Levels of MASP-2 and of the ficolin-3/MASP-2 complex were elevated (P < .0001 and .033, respectively), whereas that of FCN3-TCC was lower (P < .0001) during attacks than during the symptom-free period. During symptom-free periods, FCN3-TCC deposition was significantly related to concentrations of ficolin-3 (R = 0.2778; P = .0022), antigenic C1-INH (R = 0.3152; P = .0006), and C4 (R = 0.5307; P < .0001). Both ficolin-3 and MASP-2 levels correlated inversely with the time from the onset of the attack until blood sampling.CONCLUSIONS: There is a marked heterogeneity of the pathomechanism and development of hereditary angioedema attacks in different patients. Our results suggest that the activation of the ficolin-LP may deplete the innately low level of C1-INH and thus, it may contribute to the uncontrolled activation of plasma cascade systems, and thereby to edema formation.",
keywords = "Adult, Angioedemas, Hereditary, Complement C1 Inhibitor Protein, Complement C4, Female, Glycoproteins, Humans, Lectins, Male, Mannose-Binding Protein-Associated Serine Proteases, Middle Aged, Signal Transduction, Young Adult",
author = "Dorottya Csuka and Lea Munthe-Fog and Estrid Hein and Zsuzsanna Zotter and Zolt{\'a}n Proh{\'a}szka and Henriette Farkas and Lilian Varga and Peter Garred",
note = "Copyright {\textcopyright} 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.",
year = "2014",
month = dec,
doi = "10.1016/j.jaci.2014.05.030",
language = "English",
volume = "134",
pages = "1388–1393.e1",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "6",

}

RIS

TY - JOUR

T1 - Activation of the ficolin-lectin pathway during attacks of hereditary angioedema

AU - Csuka, Dorottya

AU - Munthe-Fog, Lea

AU - Hein, Estrid

AU - Zotter, Zsuzsanna

AU - Prohászka, Zoltán

AU - Farkas, Henriette

AU - Varga, Lilian

AU - Garred, Peter

N1 - Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

PY - 2014/12

Y1 - 2014/12

N2 - BACKGROUND: The activation of plasma enzyme systems is insufficiently controlled in hereditary angioedema due to the deficiency of C1-inhibitor (C1-INH) (HAE-C1-INH). Recently, it was suggested that the ficolin-lectin pathway (ficolin-LP) might play a more dominant role than the mannose-binding lectin-lectin pathway in the pathomechanism of HAE-C1-INH.OBJECTIVE: Because the role of the ficolin-LP during edematous attacks is still enigmatic, we analyzed its activity during such episodes.METHODS: Thirty-five patients with HAE-C1-INH, who have experienced severe attacks on 106 occasions, were enrolled. We analyzed blood samples drawn during attacks, and obtained 35 samples from the same patients during symptom-free periods. The serum levels of ficolin-2, ficolin-3, MASP-2, ficolin-3/MASP-2 complex, C1-INH, and C4, as well as the extent of ficolin-3-mediated terminal complement complex (FCN3-TCC) deposition, were measured using ELISA-based methods.RESULTS: Levels of MASP-2 and of the ficolin-3/MASP-2 complex were elevated (P < .0001 and .033, respectively), whereas that of FCN3-TCC was lower (P < .0001) during attacks than during the symptom-free period. During symptom-free periods, FCN3-TCC deposition was significantly related to concentrations of ficolin-3 (R = 0.2778; P = .0022), antigenic C1-INH (R = 0.3152; P = .0006), and C4 (R = 0.5307; P < .0001). Both ficolin-3 and MASP-2 levels correlated inversely with the time from the onset of the attack until blood sampling.CONCLUSIONS: There is a marked heterogeneity of the pathomechanism and development of hereditary angioedema attacks in different patients. Our results suggest that the activation of the ficolin-LP may deplete the innately low level of C1-INH and thus, it may contribute to the uncontrolled activation of plasma cascade systems, and thereby to edema formation.

AB - BACKGROUND: The activation of plasma enzyme systems is insufficiently controlled in hereditary angioedema due to the deficiency of C1-inhibitor (C1-INH) (HAE-C1-INH). Recently, it was suggested that the ficolin-lectin pathway (ficolin-LP) might play a more dominant role than the mannose-binding lectin-lectin pathway in the pathomechanism of HAE-C1-INH.OBJECTIVE: Because the role of the ficolin-LP during edematous attacks is still enigmatic, we analyzed its activity during such episodes.METHODS: Thirty-five patients with HAE-C1-INH, who have experienced severe attacks on 106 occasions, were enrolled. We analyzed blood samples drawn during attacks, and obtained 35 samples from the same patients during symptom-free periods. The serum levels of ficolin-2, ficolin-3, MASP-2, ficolin-3/MASP-2 complex, C1-INH, and C4, as well as the extent of ficolin-3-mediated terminal complement complex (FCN3-TCC) deposition, were measured using ELISA-based methods.RESULTS: Levels of MASP-2 and of the ficolin-3/MASP-2 complex were elevated (P < .0001 and .033, respectively), whereas that of FCN3-TCC was lower (P < .0001) during attacks than during the symptom-free period. During symptom-free periods, FCN3-TCC deposition was significantly related to concentrations of ficolin-3 (R = 0.2778; P = .0022), antigenic C1-INH (R = 0.3152; P = .0006), and C4 (R = 0.5307; P < .0001). Both ficolin-3 and MASP-2 levels correlated inversely with the time from the onset of the attack until blood sampling.CONCLUSIONS: There is a marked heterogeneity of the pathomechanism and development of hereditary angioedema attacks in different patients. Our results suggest that the activation of the ficolin-LP may deplete the innately low level of C1-INH and thus, it may contribute to the uncontrolled activation of plasma cascade systems, and thereby to edema formation.

KW - Adult

KW - Angioedemas, Hereditary

KW - Complement C1 Inhibitor Protein

KW - Complement C4

KW - Female

KW - Glycoproteins

KW - Humans

KW - Lectins

KW - Male

KW - Mannose-Binding Protein-Associated Serine Proteases

KW - Middle Aged

KW - Signal Transduction

KW - Young Adult

U2 - 10.1016/j.jaci.2014.05.030

DO - 10.1016/j.jaci.2014.05.030

M3 - Journal article

C2 - 25042985

VL - 134

SP - 1388–1393.e1

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 6

ER -

ID: 137909867