title: Product-dependent anti-factor VIII antibodies.
abstract: The development of anti-factor (F)VIII antibodies in haemophilia A (HA) subjects undergoing replacement therapy has been well documented. The correlation between antibody development and the FVIII product used for replacement therapy remains a subject of discussion. The aim of this study was to evaluate the presence of anti-FVIII antibodies towards three commercial rFVIII products in 34 HA subjects' plasmas. Antibodies were quantitated by a Multiplex Fluorescence Immunoassay. All plasmas contained anti-FVIII antibodies at variable concentrations ranging from 50 nm to 570 μm. Eleven of the 20 HA subjects treated with one (r)FVIII product contained inhibitory anti-FVIII antibodies (0.8-3584 BU). The inhibitory antibody titre and the molar concentrations of total antibody were mildly correlated (r(2) = 0.6). Pronounced differences in antibody recognition with the three rFVIII products were observed. For the group treated with Product 'A', the titre towards this product was 2.4-fold higher than that observed with another full-length rFVIII-containing product (Product 'B') and almost four-fold higher than that measured with a B domain-less rFVIII product (Product 'C'). For the group of 14 HA subjects treated with FVIII other than Product 'A', only one showed higher antibody titre when measured with this product. Our data suggest that the development of anti-FVIII antibodies is biased towards the product used for treatment and that a significant fraction of antibodies bind to the B domain of FVIII.
authors.affiliation: Department of Biochemistry, College of Medicine, University of Vermont, Burlington, VT 05446, USA.
authors.forename: S
authors.initials: S
authors.lastname: Butenas
authors.forename: J
authors.initials: J
authors.lastname: Krudysz-Amblo
authors.forename: G E
authors.initials: GE
authors.lastname: Rivard
authors.forename: K
authors.initials: K
authors.lastname: G Mann
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005169:Factor VIII / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000627:therapeutic use; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000906:Antibodies; D011994:Recombinant Proteins; D005169:Factor VIII
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