No effect of a new second-generation B-domain-deleted recombinant product on lymphocyte transformation in vitro: a study of plasma-derived and recombinant products.
Immunomodulatory effects of various factor VIII and factor IX clotting factor concentrates (CFCs) and of albumin were evaluated by a sensitive assay measuring the incorporation of 3H-thymidine in phytohaemagglutinin-stimulated lymphocytes in the presence of monodansylthiacadaverine. In contrast to previous findings by others, we found lymphocyte transformation to be inhibited by all plasma-derived factor VIII concentrates at concentrations of 0.02, 0.2 and 2.0 IU/ml, including those purified by monoclonal antibodies (P < 0.05). Kryobulin TIM3 had the most pronounced effect. In addition, three plasma-derived human albumin preparations exerted a similar inhibitory effect as the factor VIII concentrates, whereas the corresponding plasma-derived factor IX concentrates only manifested minor immunomodulatory effects. Of the recombinant preparations, only Recombinate exerted an inhibitory effect at 0.02 and 0.2 IU/ml, whereas both Kogenate and Recombinate decreased 3H-thymidine incorporation at 2.0 IU/ml (P = 0.01). No immunomodulatory effect at all was observed with r-VIII SQ, a new B-domain-deleted recombinant factor VIII preparation free from added albumin. The significance of this finding regarding immunological side-effects including inhibitor development remains to be evaluated, but this second-generation recombinant product opens up new and interesting perspectives yet to be explored.
Astermark
J
J
Department for Coagulation Disorders, University of Lund, University Hospital, Malmö, Sweden.
Ekman
M
M
Berntorp
E
E
D002103:Cadaverine / Q000031:analogs & derivatives / Q000276:immunology; D005164:Factor IX / Q000276:immunology*; D005169:Factor VIII / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology; D008213:Lymphocyte Activation / Q000502:physiology*; D010835:Phytohemagglutinins / Q000276:immunology
D007166:Immunosuppressive Agents; D010835:Phytohemagglutinins; D005169:Factor VIII; D005164:Factor IX; C008542:monodansylcadaverine; D002103:Cadaverine