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

Dorottya Csuka, Lea Munthe-Fog, Estrid Hein, Zsuzsanna Zotter, Z. Prohászka, H. Farkas, L. Varga, Peter Garred

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

MethodsThirty-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

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.

Original languageEnglish
Pages (from-to)1388-1393.e1
JournalJournal of Allergy and Clinical Immunology
Volume134
Issue number6
DOIs
Publication statusPublished - Dec 1 2014

Fingerprint

Hereditary Angioedemas
Lectins
Mannose-Binding Protein-Associated Serine Proteases
Mannose-Binding Lectin
Complement Membrane Attack Complex
Enzyme Activation
ficolin
Edema
Enzyme-Linked Immunosorbent Assay

Keywords

  • C1-inhibitor
  • edematous attack
  • ficolins
  • Hereditary angioedema
  • lectin pathway
  • MASPs

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Medicine(all)

Cite this

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

In: Journal of Allergy and Clinical Immunology, Vol. 134, No. 6, 01.12.2014, p. 1388-1393.e1.

Research output: Contribution to journalArticle

Csuka, Dorottya ; Munthe-Fog, Lea ; Hein, Estrid ; Zotter, Zsuzsanna ; Prohászka, Z. ; Farkas, H. ; Varga, L. ; Garred, Peter. / Activation of the ficolin-lectin pathway during attacks of hereditary angioedema. In: Journal of Allergy and Clinical Immunology. 2014 ; Vol. 134, No. 6. pp. 1388-1393.e1.
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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.MethodsThirty-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 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.",
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AU - Munthe-Fog, Lea

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AU - Zotter, Zsuzsanna

AU - Prohászka, Z.

AU - Farkas, H.

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AU - Garred, Peter

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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.MethodsThirty-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 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.MethodsThirty-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 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.

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