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458 Differences of Complement Activation Profile between Type I and Type II of Hereditary Angioedema Due to C1-inhibitor Deficiency
BACKGROUND: In hereditary angioedema (HAE), diverse mutations in the C1-inhibitor gene may produce either normal C1-inhibitor protein in insufficient quantities (HAE type I), or a dysfunctional protein in normal or even excessive amounts (HAE type II). Previously, we have found strong association be...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
World Allergy Organization Journal
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3513152/ http://dx.doi.org/10.1097/01.WOX.0000411573.74196.57 |
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author | Csuka, Dorottya Kelemen, Zsuzsanna Varga, Lilian Füst, George Farkas, Henriette |
author_facet | Csuka, Dorottya Kelemen, Zsuzsanna Varga, Lilian Füst, George Farkas, Henriette |
author_sort | Csuka, Dorottya |
collection | PubMed |
description | BACKGROUND: In hereditary angioedema (HAE), diverse mutations in the C1-inhibitor gene may produce either normal C1-inhibitor protein in insufficient quantities (HAE type I), or a dysfunctional protein in normal or even excessive amounts (HAE type II). Previously, we have found strong association between baseline level of functional C1-inhibitor and severity of HAE. Our aim was to investigate complement activation products in HAE, during a follow-up period, and to analyze the relationship between these products and severity of disease. METHODS: 107 HAE patients (96 HAE type I, 11 type II) and 113 healthy control subjects were included. C1rC1sC1-INH, C3bBbP, and SC5b-9 levels were determined using ELISA methods in single EDTA-plasma samples of controls and in 4 samples from patients taken in 4 subsequent years. Between-group differences were evaluated with the Mann-Whitney test, and correlations were calculated using non-parametric Spearman's correlation coefficients. RESULTS: Median levels of C1rC1sC1-INH (60 U/mL [40–113] vs 8 U/mL [4–10]; P < 0.0001) and SC5b-9 (0.6 U/mL [0.4–1.2] vs 1.8[0.9–2.8]; P < 0.0001) differed between patients and controls. Significant differences were found between HAE type I and type II as regards median C1rC1sC1-INH level (54 U/mL [33–97] vs 31 U/mL [21–49], P < 0.0001), and in an opposite manner with C3bBbP median levels (6 U/mL [4–12] vs 10 U/mL [8–17], P = 0.0002). Level of C1rC1sC1-INH correlated with the number of attacks (r = 0.3546, P = 0.0004) in HAE type I, but not in HAE type II. Dividing the patients into 2 subgroups based on danazol therapy, significant association (r = 0.3705, P = 0.0026) was found between level of C1rC1sC1-INH and annual attack number only in patients not treated with danazol. Similar results were found as regards the number of C1-inhibitor vials administered, which correlated with the level of C1rC1sC1-INH only in HAE type I (r = 0.4288, P < 0.0001) and in patients not treated with danazol (r = 0.4783, P < 0.0001). CONCLUSIONS: Monitoring the level of C1rC1sC1-INH is mostly informative in HAE type I patients, who are not treated with danazol. No correlation was found in HAE type II patients between level of C1rC1sC1-INH and disease severity markers. As this observation may be explained by the small number of HAE type II patients, multicenter studies are needed, including more HAE type II patients. |
format | Online Article Text |
id | pubmed-3513152 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | World Allergy Organization Journal |
record_format | MEDLINE/PubMed |
spelling | pubmed-35131522012-12-21 458 Differences of Complement Activation Profile between Type I and Type II of Hereditary Angioedema Due to C1-inhibitor Deficiency Csuka, Dorottya Kelemen, Zsuzsanna Varga, Lilian Füst, George Farkas, Henriette World Allergy Organ J Abstracts of the XXII World Allergy Congress BACKGROUND: In hereditary angioedema (HAE), diverse mutations in the C1-inhibitor gene may produce either normal C1-inhibitor protein in insufficient quantities (HAE type I), or a dysfunctional protein in normal or even excessive amounts (HAE type II). Previously, we have found strong association between baseline level of functional C1-inhibitor and severity of HAE. Our aim was to investigate complement activation products in HAE, during a follow-up period, and to analyze the relationship between these products and severity of disease. METHODS: 107 HAE patients (96 HAE type I, 11 type II) and 113 healthy control subjects were included. C1rC1sC1-INH, C3bBbP, and SC5b-9 levels were determined using ELISA methods in single EDTA-plasma samples of controls and in 4 samples from patients taken in 4 subsequent years. Between-group differences were evaluated with the Mann-Whitney test, and correlations were calculated using non-parametric Spearman's correlation coefficients. RESULTS: Median levels of C1rC1sC1-INH (60 U/mL [40–113] vs 8 U/mL [4–10]; P < 0.0001) and SC5b-9 (0.6 U/mL [0.4–1.2] vs 1.8[0.9–2.8]; P < 0.0001) differed between patients and controls. Significant differences were found between HAE type I and type II as regards median C1rC1sC1-INH level (54 U/mL [33–97] vs 31 U/mL [21–49], P < 0.0001), and in an opposite manner with C3bBbP median levels (6 U/mL [4–12] vs 10 U/mL [8–17], P = 0.0002). Level of C1rC1sC1-INH correlated with the number of attacks (r = 0.3546, P = 0.0004) in HAE type I, but not in HAE type II. Dividing the patients into 2 subgroups based on danazol therapy, significant association (r = 0.3705, P = 0.0026) was found between level of C1rC1sC1-INH and annual attack number only in patients not treated with danazol. Similar results were found as regards the number of C1-inhibitor vials administered, which correlated with the level of C1rC1sC1-INH only in HAE type I (r = 0.4288, P < 0.0001) and in patients not treated with danazol (r = 0.4783, P < 0.0001). CONCLUSIONS: Monitoring the level of C1rC1sC1-INH is mostly informative in HAE type I patients, who are not treated with danazol. No correlation was found in HAE type II patients between level of C1rC1sC1-INH and disease severity markers. As this observation may be explained by the small number of HAE type II patients, multicenter studies are needed, including more HAE type II patients. World Allergy Organization Journal 2012-02-17 /pmc/articles/PMC3513152/ http://dx.doi.org/10.1097/01.WOX.0000411573.74196.57 Text en Copyright © 2012 by World Allergy Organization |
spellingShingle | Abstracts of the XXII World Allergy Congress Csuka, Dorottya Kelemen, Zsuzsanna Varga, Lilian Füst, George Farkas, Henriette 458 Differences of Complement Activation Profile between Type I and Type II of Hereditary Angioedema Due to C1-inhibitor Deficiency |
title | 458 Differences of Complement Activation Profile between Type I and Type II of Hereditary Angioedema Due to C1-inhibitor Deficiency |
title_full | 458 Differences of Complement Activation Profile between Type I and Type II of Hereditary Angioedema Due to C1-inhibitor Deficiency |
title_fullStr | 458 Differences of Complement Activation Profile between Type I and Type II of Hereditary Angioedema Due to C1-inhibitor Deficiency |
title_full_unstemmed | 458 Differences of Complement Activation Profile between Type I and Type II of Hereditary Angioedema Due to C1-inhibitor Deficiency |
title_short | 458 Differences of Complement Activation Profile between Type I and Type II of Hereditary Angioedema Due to C1-inhibitor Deficiency |
title_sort | 458 differences of complement activation profile between type i and type ii of hereditary angioedema due to c1-inhibitor deficiency |
topic | Abstracts of the XXII World Allergy Congress |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3513152/ http://dx.doi.org/10.1097/01.WOX.0000411573.74196.57 |
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