THE INHIBITOR ANTIBODY-RESPONSE IS MORE COMPLEX IN HEMOPHILIA-A PATIENTS THAN IN MOST NONHEMOPHILIACS WITH FACTOR-VIII AUTOANTIBODIES

Approximately 25% of hemophilia A patients infused with factor VIII (f VIII) mount an immune response, which leads to its inactivation. Anti- fVIII autoantibodies are also seen rarely in individuals with normal f VIII, We have previously demonstrated that some anti-A2 and anti-C2 do main antibodies are fVIII inhibitors and that many patients have addit ional inhibitors with a fVIII light chain (LCh) epitope outside C2. Be cause the contribution of the different antibodies to the plasma inhib itor titer had been examined in a limited number of patients (14), we report in this study a more extensive analysis of 55 plasmas, The domi nant inhibitors in 62% (13 of 21) of autoantibody plasmas were directe d only against C2 or A2, but not both, whereas this pattern was found in only 15% (5 of 34) of hemophilic plasmas. In addition, anti-A2 inhi bitors were present in 71% (24 of 34) of hemophilic plasmas, but only 33% (7 of 21) of autoantibody plasmas. These results demonstrated that the inhibitor response In hemophiliacs was more complex and the epito pe specificity was somewhat different. A comparison of hemophiliacs tr eated only with plasma fVIII or recombinant fVIII showed no significan t differences in the complexity of the inhibitor response, as greater than or equal to 2 different inhibitor antibodies were present in 78% (18 of 23) of the former and 82% (9 of 11) of the latter. In contrast, the major inhibitors in 35% (8 of 23) of hemophiliacs treated with pl asma fVIII were directed against C2 and another LCh epitope within res idues 1649-2137, but not A2, while none (0 of 11) treated with recombi nant fVIII had this pattern. (C) 1997 by The American Society of Hemat ology.