[Characterization of factor VIII antibody epitopes from haemophilia A patients using cellulose bound FVIII peptide libraries].
Approximately 30% of patients suffering from severe haemophilia A develop antibodies against factor VIII (FVIII) neutralizing the effect of the pro-coagulant activity of intravenously injected FVIII as a complication of replacement therapy. Generally, various epitopes on the FVIII molecule are bound by these antibodies. The detailed structure of such epitopes is unknown. In this study epitopes on the FVIII molecule are identified using solid phase bound peptide arrays carrying the whole amino acid sequence of FVIII as small oligopeptides. The binding of FVIII antibodies by specific peptide sequences on the array indicates potential epitopes. FVIII antibodies of inhibitor patients and healthy blood donors are currently investigated by this method. Identified epitopes may lead to new concepts in therapy aiming at avoidance of inhibitor formation or improvement of inhibitor eradication. As participant of the 'haemophilia A' consortium dealing with genotype/phenotype correlation in haemophilia A we investigate, if the site or type of the mutation correlates with the epitopes, and if there is any relation between epitopes and clinical course. Furthermore, the influence of epitopes on therapeutical effects and the outcome of immune tolerance induction is under scrutiny.
Albert
T
T
Institut für experimentelle Hämatologie und Transfusionsmedizin, Universitätsklinikum Bonn.
Lange
S
S
Oldenburg
J
J
Graw
J
J
Schramm
W
W
Hanfland
P
P
Brackmann
H-H
HH
Schwaab
R
R
D001323:Autoantibodies / Q000097:blood*; D001782:Blood Donors; D000939:Epitopes / Q000097:blood*; D005169:Factor VIII / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D005838:Genotype; D006467:Hemophilia A / Q000097:blood / Q000276:immunology* / Q000628:therapy; D006801:Humans; D019151:Peptide Library; D010641:Phenotype; D012016:Reference Values
D001323:Autoantibodies; D000939:Epitopes; D019151:Peptide Library; D005169:Factor VIII