Acquired C 1 Inhibitor ( Cl - INH ) Deficiency Type

The response of two patients with autoantibody-mediated Clinhibitor (Cl-INH) deficiency to replacement therapy with Cl-INH was studied over a period of 3 d. In patient 1 an acute attack of angioedema was successfully managed by infusion of 1,000 U ofC1-INH concentrate. C1-INH function returned to normal levels within 30 min., while CH50 and C4 peaked after 6-7 h and Cl hemolytic activity reached 50-60% of normal after 3 d. Immediately after the injection an increase in ClINH-anti-C-INH complexes was observed. Based on NHr terminal sequence analysis ofthe patients' M, 96,000 C1-INH, it is concluded that this fragment is generated after cleavage of C1-INH in its active site by one of its target proteases without generating a covalent Cl-INH-enzyme complex. In a second patient with a four to five times higher anti-Cl-INH antibody titer, the infusion of500 ml ofplasma or of 2,000 U ofC1-INH concentrate influenced neither the severity of the patient's angioedema nor the tested parameters, except for an increase in the amount of Cl-INH-anti-Cl-INH complexes. Analysis of patients' anti-Ci-INH antibodies revealed that the antibodies recognize different epitopes within the C1-INH. This suggests that patients with acquired angioedema type HI are a heterogenous group with respect to the C1-INH autoantibodies.