Acquired C1 inhibitor (C1-INH) deficiency type II. Replacement therapy with C1-INH and analysis of patients' C1-INH and anti-C1-INH autoantibodies.
The response of two patients with autoantibody-mediated C1-inhibitor (C1-INH) deficiency to replacement therapy with C1-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 of C1-INH concentrate. C1-INH function returned to normal levels within 30 min, while CH50 and C4 peaked after 6-7 h and C1 hemolytic activity reached 50-60% of normal after 3 d. Immediately after the injection an increase in C1-INH-anti-C1-INH complexes was observed. Based on NH2-terminal sequence analysis of the patients' Mr 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 C1-INH-enzyme complex. In a second patient with a four to five times higher anti-C1-INH antibody titer, the infusion of 500 ml of plasma or of 2,000 U of C1-INH concentrate influenced neither the severity of the patient's angioedema nor the tested parameters, except for an increase in the amount of C1-INH-anti-C1-INH complexes. Analysis of patients' anti-C1-INH antibodies revealed that the antibodies recognize different epitopes within the C1-INH. This suggests that patients with acquired angioedema type II are a heterogenous group with respect to the C1-INH autoantibodies.
Alsenz
J
J
Institute of Medical Microbiology, Johannes-Gutenberg University, Mainz, Federal Republic of Germany.
Lambris
J D
JD
Bork
K
K
Loos
M
M
D000595:Amino Acid Sequence; D000799:Angioedema / Q000097:blood / Q000628:therapy*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000032:analysis*; D001327:Autoimmune Diseases / Q000097:blood / Q000628:therapy*; D003174:Complement C1 Inactivator Proteins / Q000172:deficiency* / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D008969:Molecular Sequence Data
D001323:Autoantibodies; D003174:Complement C1 Inactivator Proteins