Inhibitors in German hemophilia A patients treated with a double virus inactivated factor VIII concentrate bind to the C2 domain of FVIII light chain.
To reduce the risk of transmission of hepatitis A virus, an Octapharma produced factor VIII (fVIII) concentrate treated with solvent detergent (FVIII-SD) was further pasteurized after purification. This product, Octavi SDPlus (FVIII-SDP), was marketed in Europe in 1993 to 1995. Inhibitors appeared from September to October, 1995, in 12 of 109 previously treated German hemophilia A patients. A study of similarly treated Belgian patients, who also developed inhibitors, had shown antibodies to the fVIII light chain (domains A3-C1-C2) only. In the present study, the epitope specificity of 8 German inhibitor plasmas was also found to be restricted to the light chain. In radioimmunoprecipitation assays to localize the light chain epitope(s), antibody binding to heavy chain (domains A1-A2-B) was 11-148 fold lower than to the C2 domain, and binding to recombinant A3-C1 was barely detectable. These results were supported by >95% neutralization of a high responder inhibitor titer by the C2 domain.
Laub
R
R
Red Cross, Brussels, Belgium.
Di Giambattista
M
M
Fondu
P
P
Brackmann
H H
HH
Lenk
H
H
Saenko
E L
EL
Felch
M
M
Scandella
D
D
D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000276:immunology; D000918:Antibody Specificity; D002648:Child; D005169:Factor VIII / Q000276:immunology* / Q000627:therapeutic use*; D005858:Germany; D006467:Hemophilia A / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D011863:Radioimmunoassay; D014780:Viruses