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.
In: The Journal of allergy and clinical immunology, Vol. 134, No. 6, 12.2014, p. 1388–1393.e1.Research output: Contribution to journal › Journal article › Research › peer-review
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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