[Factor VIII epitopes recognized by inhibitors in hemophiliacs]

A 44-year-old male hemophiliac with high titer anti-factor VIII antibody (66 bethesda units/ml) was admitted on November 11, 1989 because of epigastralgia and melena. A gastric ulcer with a spurting artery was revealed by an upper gastrointestinal endoscopy. Infusion of activated prothrombin complex concentrates and endoscopical ethanol injection to the bleeding vessel were ineffective. After clipping of the vessel, the bleeding was completely ceased. The inhibitor antibody was purified by Sephacryl S 200 and Protein A cellulofine column chromatography. Purified IgG showed factor VIII inhibitor activity. Factor VIII epitopes recognized by the inhibitors was examined by western blotting. Factor VIII concentrate purified by the antigen. This factor VIII preparation was composed of a doublet of light chains (M.W. 80 kD) and 3 heavy chains (M.W. 160-200 kD) when examined by SDS-PAGE followed by immunoblotting using monoclonal antibodies against factor VIII light and heavy chains. The inhibitor in this case reacted to the heavy chains of factor VIII, whereas antifactor VIII antibody in the other case reacted to the light chain of factor VIII.