aInstitute of Molecular and Cell Biology, University of Tartu, Riia 23, Tartu, 51010, Estonia
bInstitute of Zoology and Hydrobiology, University of Tartu, Vanemuise 46, Tartu, 51014, Estonia
cEstonian Biocentre, Riia 23A, Tartu, Estonia
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-β1) 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-β1 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-β1 present in plasma-derived FVIII preparations reduce the immune response against FVIII. However, we cannot exlude possible modulatory effects of other plasma proteins.