Parameters of the classical complement pathway predict disease severity in hereditary angioedema

Functional C1-inhibitor (C1-inh) and C4 are potential severity markers of hereditary angioedema due to deficiency of C1-inh (HAE-C1-inh), and the complexes generated through complement activation may be relevant.We studied the association between disease severity and complement parameters in 105 HAE-C1-inh patients. Disease severity was characterized by the number of angioedema attacks or alternatively, by the number of C1-inh concentrate ampoules (C1-inh-amp) used for the treatment of attacks.Median C1rC1sC1-inh level was higher (32.8 U/ml vs. 3.4 U/ml; p < 0.0001) in patients, compared to controls. C1rC1sC1-inh and C1-inh strongly correlated with attack number and C1-inh-amp, both in the whole patient population and in the subgroup on danazol prophylaxis. Both C1rC1sC1-inh and C1-inh are suitable for predicting disease severity based on attack frequency and C1-inh-amp (OR = 4.38[1.43-13.43], p = 0.010 and 11.78[2.54-54.67], p = 0.002, respectively).We presume that both C1rC1sC1-inh and C1-inh might prove sensitive predictors of the severity of HAE-C1-inh.