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The inhibitor antibody response is more complex in hemophilia A patients
than in most nonhemophiliacs with factor VIII autoantibodies. Recombinate
and Kogenate Study Groups
R Prescott, H Nakai, EL Saenko, I Scharrer, IM Nilsson, JE Humphries, D Hurst, G Bray and D Scandella
American Red Cross, Rockville, MD 20855, USA.
Approximately 25% of hemophilia A patients infused with factor VIII (fVIII)
mount an immune response, which leads to its inactivation. Anti- fVIII
autoantibodies are also seen rarely in individuals with normal fVIII. We
have previously demonstrated that some anti-A2 and anti-C2 domain
antibodies are fVIII inhibitors and that many patients have additional
inhibitors with a fVIII light chain (LCh) epitope outside C2. Because the
contribution of the different antibodies to the plasma inhibitor titer had
been examined in a limited number of patients (14), we report in this study
a more extensive analysis of 55 plasmas. The dominant inhibitors in 62% (13
of 21) of autoantibody plasmas were directed 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 inhibitors 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 epitope specificity was somewhat different. A comparison of
hemophiliacs treated only with plasma fVIII or recombinant fVIII showed no
significant differences in the complexity of the inhibitor response, as
> or = 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 plasma fVIII were
directed against C2 and another LCh epitope within residues 1649-2137, but
not A2, while none (0 of 11) treated with recombinant fVIII had this
pattern.
Volume 89,
Issue 10,
pp. 3663-3671,
05/15/1997
Copyright © 1997 by The American Society of Hematology
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