Complement testing in angioedema and hemolytic anemia
In unexplained angioedema it is important to consider C1-inhibitor (C1-INH) deficiency. Deficiency of C1-INH deficiency can be genetically determined that is hereditary or acquired.
Hereditary angioedema (HAE) is caused by a mutation in the serping1 gene coding for C1-INH. The mutation affects one of the C1-INH genes implying that HAE is a heterozygous disease with dominant inheritance (homozygous cases are very rare, reported in two families).Two forms of HAE are distinguished; type I (about 85% of cases) there the mutated gene give rise to no protein and type II there the mutation results in production of a dysfunctional protein. A large number of different mutations have been reported. In both types there is one normal gene which results in synthesis of C1-INH (ref 1). A new form of HAE with normal C1INH was first described in 2000 and is sometimes referred to as HAE type III (ref 2).
Acquired angioedema (AAE) due to C1-INH deficiency occur typically in patients with lymphoproliferative disease. In some cases antibodies against C1-INH are found.
In both HAE and AAE an increased activation of mainly the classical pathway is seen which generally results in a low C4 level. Analysis of complement including functional assays gives the diagnose C1-INH-deficiency. Results should be confirmed in a second sample.