title: Analysis of factor VIII inhibitors in a haemophilia A patient with an Arg593-->Cys mutation using phage display.
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.
authors.affiliation: Department of Plasma Proteins, Sanquin Research at CLB, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Bril
authors.forename: Ellen A M
authors.initials: EA
authors.lastname: Turenhout
authors.forename: Paul H P
authors.initials: PH
authors.lastname: Kaijen
authors.forename: Edward N
authors.initials: EN
authors.lastname: van den Brink
authors.forename: Maria M W
authors.initials: MM
authors.lastname: Koopman
authors.forename: Marjolein
authors.initials: M
authors.lastname: Peters
authors.forename: Jan
authors.initials: J
authors.lastname: Voorberg
mesh_terms: D000595:Amino Acid Sequence; D000906:Antibodies / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D019774:Blood Coagulation Factor Inhibitors / Q000235:genetics*; D005169:Factor VIII / Q000037:antagonists & inhibitors*; D006467:Hemophilia A / Q000097:blood / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007156:Immunologic Memory; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D019151:Peptide Library
chemical_list: D000906:Antibodies; D019774:Blood Coagulation Factor Inhibitors; D007143:Immunoglobulin Heavy Chains; D019151:Peptide Library; D005169:Factor VIII