title: Comparison of the immunogenicity of different therapeutic preparations of human factor VIII in the murine model of hemophilia A.
abstract: Von Willebrand factor (VWF) has been proposed to reduce the immunogenicity of therapeutic factor VIII (FVIII) in patients with hemophilia A. Using FVIII-deficient mice, we compared the immunogenicity of different preparations of plasma-derived (pd) and recombinant (r) FVIII. Treatment of mice with pdFVIII induced significantly lower titers of FVIII inhibitors, as measured by ELISA and in vitro coagulation assays, compared with rFVIII. Furthermore, pre-incubation of rFVIII with excess VWF significantly reduced rFVIII immunogenicity. Our data confirm that pdFVIII induces lower levels of inhibitors than rFVIII, and that VWF is an immuno-chaperone molecule for FVIII.
authors.affiliation: Centre de Recherche des Cordeliers, Université Pierre et Marie Curie - Paris 6, UMR S 872, Paris, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Delignat
authors.forename: Suryasarathi
authors.initials: S
authors.lastname: Dasgupta
authors.forename: Sébastien
authors.initials: S
authors.lastname: André
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Navarrete
authors.forename: Srinivas V
authors.initials: SV
authors.lastname: Kaveri
authors.forename: Jagadeesh
authors.initials: J
authors.lastname: Bayry
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: André
authors.forename: Sami
authors.initials: S
authors.lastname: Chtourou
authors.forename: Zéra
authors.initials: Z
authors.lastname: Tellier
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lacroix-Desmazes
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005169:Factor VIII / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use*; D005260:Female; D006467:Hemophilia A / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D051379:Mice
chemical_list: D007074:Immunoglobulin G; D005169:Factor VIII