ANTI-FACTOR-VIII INHIBITOR ALLOANTIBODIES RECOGNIZING THE A2-DOMAIN IN THE HUMAN FACTOR-VIII HEAVY-CHAIN POORLY BIND TO PORCINE FACTOR-VIII

Anti-factor VIII (FVIII) inhibitor alloantibodies from 11 patients wit h hemophilia A, along with five anti-FVIII neutralizing monoclonal ant ibodies, were examined for differences in their reactivities with the A2 and C2 domains of human and porcine FVIII. None of the patients had been previously treated with porcine FVIII. Six inhibitors which spec ifically recognized the human FVIII C2 domain bound to both the 76-kDa porcine FVIII light chain and its 69-kDa proteolyzed fragments, showi ng cross-reactivity against porcine FVIII between 33 and 100%. Two A2- specific inhibitors did not react with porcine FVIII. The cross-reacti vity was low (0-0.5%). The inhibitors recognizing both C2 and A2 react ed with the 76- and 69-kDa bands of porcine FVIII light chain, with cr oss-reactivity of between 11 and 33%. Monoclonal antibodies recognizin g A1 (C-5) and A2 (JR8) did not react with the porcine FVIII. No anti- porcine FVIII neutralizing activity was detected in these antibodies. Monoclonal antibodies to the amino-terminal portion of A3 (NMC-VIII/10 and C-2) poorly reacted with the 76-kDa band, the cross-reactivities being 0 and 0.5%, respectively. NMC-VIII/5 recognizing C2 which compet es with the C2-specific inhibitor, reacted with both the 76- and 69-kD a fragments showing cross-reactivity of 13%. These findings suggest th at porcine A2 is antigenically different from human A2. The A2-specifi c inhibitor is a useful indicator for therapy with porcine FVIII. (C) 1997 Elsevier Science Ireland Ltd.