title: Inhibitors in German hemophilia A patients treated with a double virus inactivated factor VIII concentrate bind to the C2 domain of FVIII light chain.
abstract: 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.
authors.affiliation: Red Cross, Brussels, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Laub
authors.forename: M
authors.initials: M
authors.lastname: Di Giambattista
authors.forename: P
authors.initials: P
authors.lastname: Fondu
authors.forename: H H
authors.initials: HH
authors.lastname: Brackmann
authors.forename: H
authors.initials: H
authors.lastname: Lenk
authors.forename: E L
authors.initials: EL
authors.lastname: Saenko
authors.forename: M
authors.initials: M
authors.lastname: Felch
authors.forename: D
authors.initials: D
authors.lastname: Scandella
mesh_terms: 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