Comparison of the immunogenicity of different therapeutic preparations of human factor VIII in the murine model of hemophilia A
Autor: | Sandrine Delignat, Sébastien Lacroix-Desmazes, Jagadeesh Bayry, Ana-Maria Navarrete, Zera Tellier, Sébastien André, Suryasarathi Dasgupta, Marie-Hélène André, Srinivas V. Kaveri, Sami Chtourou |
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Rok vydání: | 2007 |
Předmět: |
Male
congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty animal diseases Hemophilia A law.invention Mice Immune system Von Willebrand factor law hemic and lymphatic diseases Internal medicine Coagulopathy medicine Animals Humans Hematology Factor VIII biology business.industry Immunogenicity medicine.disease In vitro Disease Models Animal Coagulation Immunoglobulin G Immunology biology.protein Recombinant DNA Female business |
Zdroj: | Haematologica. 92(10) |
ISSN: | 1592-8721 |
Popis: | 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. |
Databáze: | OpenAIRE |
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