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 hemophilic plasmas, but only 33% (7 of 21) of autoantibody factor VIII (fVIII) mount an immune response, which leads plasmas. These results demonstrated that the inhibitor reto its inactivation. Anti-fVIII autoantibodies are also seen sponse in hemophiliacs was more complex and the epitope rarely in individuals with normal fVIII. We have previously specificity was somewhat different. A comparison of hemodemonstrated that some anti-A2 and anti-C2 domain antiphiliacs treated only with plasma fVIII or recombinant fVIII bodies are fVIII inhibitors and that many patients have addishowed no significant differences in the complexity of the tional inhibitors with a fVIII light chain (LCh) epitope outside inhibitor response, ası 2 different inhibitor antibodies were C2. Because the contribution of the different antibodies to present in 78% (18 of 23) of the former and 82% (9 of 11) of the plasma inhibitor titer had been examined in a limited the latter. In contrast, the major inhibitors in 35% (8 of 23) number of patients (14), we report in this study a more exof hemophiliacs treated with plasma fVIII were directed tensive analysis of 55 plasmas. The dominant inhibitors in against C2 and another LCh epitope within residues 164962% (13 of 21) of autoantibody plasmas were directed only 2137, but not A2, while none (0 of 11) treated with recombiagainst C2 or A2, but not both, whereas this pattern was nant fVIII had this pattern. found in only 15% (5 of 34) of hemophilic plasmas. In addiq 1997 by The American Society of Hematology. tion, anti-A2 inhibitors were present in 71% (24 of 34) of