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  • Title: von Willebrand factor and transforming growth factor-beta modulate immune response against coagulation factor VIII in FVIII-deficient mice.
    Author: Kallas A, Kuuse S, Maimets T, Pooga M.
    Journal: Thromb Res; 2007; 120(6):911-9. PubMed ID: 17376515.
    Abstract:
    In up to 25% haemophilia A patients, the administration of coagulation factor VIII (FVIII) preparations for treatment of haemorrhages results in production of factor VIII specific antibodies. Plasma-derived FVIII preparations contain other plasma proteins, which may modulate the immune response to FVIII. We used FVIII-deficient mice to assess the role of von Willebrand factor (VWF) and cytokine transforming growth factor beta-1 (TGF-beta1) in the immune response against FVIII. Using the FVIII and FVIII in complex with VWF purified from the plasma-derived FVIII preparation, we demonstrated that a lower concentration of FVIII antibody was induced in FVIII-VWF-treated mice compared to FVIII-treated mice (p<0.05). The addition of recombinant latent TGF-beta1 to FVIII decreased the antibody response against FVIII compared to FVIII treatment alone (p<0.01). The obtained results suggest that VWF and latent TGF-beta1 present in plasma-derived FVIII preparations reduce the immune response against FVIII. However, we cannot exlude possible modulatory effects of other plasma proteins.
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