Analysis of factor VIII inhibitors using hybrid human/porcine factor VIII.
Recombinant hybrid human/porcine factor VIII molecules have been used to map a major determinant of the epitope recognized by human anti-factor VIII A2 domain inhibitory antibodies to a region bounded by human fVIII residues Arg484-Ile508. This approach is being used to characterize the C2 domain inhibitor epitope. The process of creating hybrid human/porcine factor VIII molecules to map inhibitor epitopes produces procoagulantly active fVIII with reduced reactivity with clinically significant factor VIII inhibitors. This suggests that it may be possible to develop of a hybrid human/porcine factor VIII that is useful in the management of hemophilia A and acquired hemophilia.
Lollar
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Department of Medicine, Emory University, Atlanta, GA 30322, USA. jlollar@unix.cc.emory.edu
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D002872:Chromosome Deletion; D018604:Epitope Mapping; D005169:Factor VIII / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000627:therapeutic use; D013552:Swine
D011994:Recombinant Proteins; D005169:Factor VIII