Comparison of the immunogenicity of different therapeutic preparations of human factor VIII in the murine model of hemophilia A.
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.
Delignat
Sandrine
S
Centre de Recherche des Cordeliers, Université Pierre et Marie Curie - Paris 6, UMR S 872, Paris, France.
Dasgupta
Suryasarathi
S
André
Sébastien
S
Navarrete
Ana-Maria
AM
Kaveri
Srinivas V
SV
Bayry
Jagadeesh
J
André
Marie-Hélène
MH
Chtourou
Sami
S
Tellier
Zéra
Z
Lacroix-Desmazes
Sébastien
S
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
D007074:Immunoglobulin G; D005169:Factor VIII