FACTOR-IX INHIBITION AND EPITOPE LOCALIZATION OF FACTOR-IX INHIBITOR ANTIBODIES IN HEMOPHILIA-B PATIENTS WITH ANAPHYLACTOID REACTIONS

We describe the results of immunological studies, reaction kinetics an d epitope localization of six inhibitor antibodies to factor IX (FIX) developed in severe haemophilia B patients. Three of the six patients had suffered recent anaphylactoid reactions to FIX concentrates, two o thers had in the past and one had none. All six inhibitors rapidly ina ctivated FIX activity in vitro, and the prominent immunoglobulin (IgG) subclass of the antibody was IgG4 when analysed with ELISA. Interesti ngly, we found an additional IgG1 component in the antibody samples fr om the patients who had recently experienced anaphylactoid reactions t o FIX. When analysed with Western blotting in these three patients, th e IgG4 antibody bound with enhanced affinity to the heavy chain or the light chain of FIX, and in two of the three the IgG1 antibody also bo und strongly to the FIX heavy chain. The results suggest that the heav y chain of FIX might play a more significant role than the light chain in the pathogenesis of anaphylactoid reactions in haemophilia B patie nts with FIX inhibitors.