Wednesday, 7 December 2011
Poster Hall (Cancún Center)
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 two 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).
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 two 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.