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 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.