von Willebrand factor and transforming growth factor-beta modulate immune response against coagulation factor VIII in FVIII-deficient mice.
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.
Kallas
Ade
A
Institute of Molecular and Cell Biology, University of Tartu, Riia 23, Tartu, 51010, Estonia. Ade.Kallas@ut.ee
Kuuse
Sulev
S
Maimets
Toivo
T
Pooga
Margus
M
D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000097:blood; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D002845:Chromatography; D005169:Factor VIII / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D006467:Hemophilia A / Q000188:drug therapy* / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D013154:Spleen / Q000166:cytology; D053773:Transforming Growth Factor beta1 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D014841:von Willebrand Factor / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology
D000906:Antibodies; D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D053773:Transforming Growth Factor beta1; D014841:von Willebrand Factor; D005169:Factor VIII