The inhibitor antibody response is more complex in hemophilia A patients than in most nonhemophiliacs with factor VIII autoantibodies. Recombinate and Kogenate Study Groups.
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.
Prescott
R
R
American Red Cross, Rockville, MD 20855, USA.
Nakai
H
H
Saenko
E L
EL
Scharrer
I
I
Nilsson
I M
IM
Humphries
J E
JE
Hurst
D
D
Bray
G
G
Scandella
D
D
D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005169:Factor VIII / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use; D006467:Hemophilia A / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use
D001323:Autoantibodies; D000939:Epitopes; D007518:Isoantibodies; D011994:Recombinant Proteins; C078147:F8 protein, human; D005169:Factor VIII