Hemophilia A is an X-linked recessive congenital
bleeding disorder. Exogenous infusion of FVIII is the treatment of choice, and the development of
immunoglobulins against FVIII (inhibitors) remains the major challenge in clinical management of the disease. Here, we investigated the effect of co-administration of FVIII with
intravenous immunoglobulin (
IVIG) on the development of inhibitors in previously untreated
hemophilia A mice. A group of
hemophilia A mice (C57BL/6FVIII-/-) received weekly
injections of recombinant human FVIII (rFVIII) for twelve consecutive weeks while a second group received co-
injections of rFVIII + IVIG. An in-house
enzyme-linked
immunosorbent assay (ELISA) was designed to detect
antibodies to rFVIII. Every mouse in the first group developed
antibodies to rFVIII. In contrast, mice treated with rFVIII + IVIG showed significantly lower antibody titers. Interestingly, when co-administration of
IVIG was discontinued after 12 weeks in some mice (rFVIII continued), these mice experienced an increase in antibody titer. In contrast, mice that continued to receive rFVIII + IVIG retained significantly lower titers. In conclusion, prophylactic rFVIII co-administration with
IVIG modulated the immune response to FVIII and resulted in decreased anti-FVIII antibody titer. These findings suggest that co-injection
therapy with
IVIG could potentially be effective in the management of
hemophilia A patients at risk of inhibitor development.