Analysis of factor VIII inhibitors in a haemophilia A patient with an Arg593-->Cys mutation using phage display

Br J Haematol. 2002 Nov;119(2):393-6. doi: 10.1046/j.1365-2141.2002.03856.x.

Abstract

We characterized anti-factor VIII antibodies in a mild haemophilia A patient with an Arg593-->Cys mutation in the A2 domain, using V gene phage-display technology. All isolated single-chain variable-domain antibody fragments were directed against residues Arg484-Ile508, a binding site for factor VIII inhibitors in the A2 domain. After a further period of replacement therapy, a transient rise in inhibitor titre was observed. These antibodies were directed against the A2 domain. Activation of a pre-existing pool of B cells, which express antibodies against residues Arg484-Ile508, could explain the rapid anamnestic response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antibodies / analysis
  • B-Lymphocytes / immunology
  • Base Sequence
  • Blood Coagulation Factor Inhibitors / genetics*
  • Factor VIII / antagonists & inhibitors*
  • Hemophilia A / blood
  • Hemophilia A / genetics*
  • Hemophilia A / immunology
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Immunologic Memory
  • Male
  • Molecular Sequence Data
  • Mutation
  • Peptide Library

Substances

  • Antibodies
  • Blood Coagulation Factor Inhibitors
  • Immunoglobulin Heavy Chains
  • Peptide Library
  • Factor VIII