Haematologica, Vol 92, Issue 10, 1423-1426 doi:10.3324/haematol.11438
Copyright © 2007 by Ferrata Storti Foundation
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Disorders of Hemostasis

Comparison of the immunogenicity of different therapeutic preparations of human factor VIII in the murine model of hemophilia A

Sandrine Delignat, Suryasarathi Dasgupta, Sébastien André, Ana-Maria Navarrete, Srinivas V. Kaveri, Jagadeesh Bayry, Marie-Hélène André, Sami Chtourou, Zéra Tellier, Sébastien Lacroix-Desmazes

From Centre de Recherche des Cordeliers, Université Pierre et Marie Curie - Paris 6, UMR S 872, Paris, France (SD, SD, SA, A-MN, SVK, JB, SL-D); Université Paris Descartes, UMR S 872, Paris, France (SD, SD, SA, A-MN, SVK, JB, SL-D; INSERM, U872, Paris, France (SD, SD, SA, A-MN, SVK, JB, SL-D, LFB, Les Ulis, France (M-HA, SC, ZT)

Correspondence: Sébastien Lacroix-Desmazes, INSERM UMRS 681, Centre de recherche des Cordeliers, 15, rue de l’Ecole de Médecine, 75006, Paris, France. E-mail: sebastien.lacroix-des-mazes{at}umrs681.jussieu.fr

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.

Key words: factor VIII, FVIII inhibitors, von Willebrand factor, animal model, hemophilia A.




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