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Analysis of factor VIII inhibitors in a haemophilia A patient with an Arg 593 →Cys mutation using phage display
Author(s) -
Bril Wendy S.,
Turenhout Ellen A. M.,
Kaijen Paul H. P.,
Van Den Brink Edward N.,
Koopman Maria M. W.,
Peters Marjolein,
Voorberg Jan
Publication year - 2002
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2002.03856.x
Subject(s) - antibody , phage display , mutation , haemophilia b , haemophilia a , haemophilia , immunoglobulin light chain , microbiology and biotechnology , factor ix , binding domain , chemistry , gene , medicine , binding site , biology , immunology , biochemistry , genetics
Summary. We characterized anti‐factor VIII antibodies in a mild haemophilia A patient with an Arg 593 →Cys mutation in the A2 domain, using V gene phage‐display technology. All isolated single‐chain variable‐domain antibody fragments were directed against residues Arg 484 ‐Ile 508 , 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 Arg 484 ‐Ile 508 , could explain the rapid anamnestic response.