R. Laub et al., Inhibitors in German hemophilia A patients treated with a double virus inactivated factor VIII concentrate bind to the C2 domain of FVIII light chain, THROMB HAEM, 81(1), 1999, pp. 39-44
To reduce the risk of transmission of hepatitis A virus, an Octapharma prod
uced 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 f
rom September to October, 1995, in 12 of 109 previously treated German hemo
philia A patients. A study of similarly treated Belgian patients, who also
developed inhibitors, had shown antibodies to the fVIII light chain (domain
s 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 r
adioimmunoprecipitation assays to localize the light chain epitope(s), anti
body 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, The
se results were supported by >95% neutralization of a high responder inhibi
tor titer by the C2 domain.