Mechanisms of action of immune tolerance induction against factor VIII in patients with congenital haemophilia A and factor VIII inhibitors.
In its most severe form, haemophilia A is a life-threatening haemorrhagic bleeding disorder that is caused by mutations in the factor VIII (FVIII) gene. About 25% of patients who receive replacement therapy with intravenous FVIII products develop neutralising antibodies (FVIII inhibitors) that inhibit the function of substituted FVIII. Long-term application of high or low doses of FVIII has evolved as an effective strategy for eradicating antibodies and inducing long-lasting immune tolerance. Despite clinical experience with the therapy, little is known about the immunological mechanisms that cause the down modulation of FVIII-specific immune responses or the induction of long-lasting immune tolerance against FVIII. This review summarises current knowledge of the immunological mechanisms that might be involved in the induction of immune tolerance against FVIII in patients with haemophilia A who have FVIII inhibitors. In addition to data from patients with haemophilia A, data from patients who have had organ transplants or have immune-related disorders, such as autoimmune diseases, are considered as well as data from animal models.
Reipert
Birgit M
BM
Baxter BioScience, Vienna, Austria. birgit_reipert@baxter.com
van Helden
Pauline M W
PM
van den Helden
Pauline M W
PM
Schwarz
Hans-Peter
HP
Hausl
Christina
C
D000818:Animals; D000917:Antibody Formation; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D019774:Blood Coagulation Factor Inhibitors / Q000276:immunology*; D003029:Coagulants / Q000627:therapeutic use; D005169:Factor VIII / Q000276:immunology* / Q000627:therapeutic use; D006467:Hemophilia A / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007108:Immune Tolerance; D007156:Immunologic Memory; D023421:Models, Animal
D001323:Autoantibodies; D019774:Blood Coagulation Factor Inhibitors; D003029:Coagulants; D005169:Factor VIII