Elimination of a major inhibitor epitope in factor...[J Biol Chem. 1994]

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1: J Biol Chem. 1994 Mar 25;269(12):8639-41. Links

Elimination of a major inhibitor epitope in factor VIII.

Lubin IM, Healey JF, Scandella D, Runge MS, Lollar P.

Department of Medicine, Emory University, Atlanta, Georgia 30322.

The A2 and C2 domains of human blood coagulation factor VIII (fVIII) contain the epitopes targeted by most inhibitory allo- and autoantibodies. Human inhibitors usually display limited or no reaction with porcine fVIII. We constructed an active, recombinant hybrid human/porcine fVIII molecule by replacing the putative human fVIII A2 domain epitope with the homologous porcine sequence. The hybrid retained full activity in the presence of antibodies with specificity restricted to the human A2 epitope. In contrast, the hybrid was neutralized by an anti-C2 antibody. These findings provide a basis for fine epitope mapping and for therapy of the inhibitor patient.

PMID: 7510693 [PubMed - indexed for MEDLINE]

Residues Glu2181-Val2243 contain a major determinant of the inhibitory epitope in the C2 domain of human factor VIII. [Blood. 1998]
Residues 484-508 contain a major determinant of the inhibitory epitope in the A2 domain of human factor VIII. [J Biol Chem. 1995]
ReviewMapping factor VIII inhibitor epitopes using hybrid human/porcine factor VIII molecules. [Haematologica. 2000]
ReviewAnalysis of factor VIII inhibitors using hybrid human/porcine factor VIII. [Thromb Haemost. 1997]
Analysis of the human factor VIII A2 inhibitor epitope by alanine scanning mutagenesis. [J Biol Chem. 1997]

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Elimination of a major inhibitor epitope in factor VIII.

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