Acquired C1 inhibitor (C1-INH) deficiency type II. Replacement therapy with C1-INH and analysis of patients' C1-INH and anti-C1-INH autoantibodies

J Clin Invest. 1989 Jun;83(6):1794-9. doi: 10.1172/JCI114084.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Angioedema / blood
  • Angioedema / therapy*
  • Antibody Specificity
  • Autoantibodies / analysis*
  • Autoimmune Diseases / blood
  • Autoimmune Diseases / therapy*
  • Complement C1 Inactivator Proteins / deficiency*
  • Complement C1 Inactivator Proteins / immunology
  • Complement C1 Inactivator Proteins / therapeutic use
  • Humans
  • Infusions, Intravenous
  • Molecular Sequence Data

Substances

  • Autoantibodies
  • Complement C1 Inactivator Proteins