Immunological aspects of inhibitor development.
The development of inhibitor antibodies is perhaps the most serious complication of coagulation factor replacement therapy. A complex interaction of several variables leads to inhibitor formation in congenital haemophilia, while acquired haemophilia represents a failure of the immune tolerance mechanisms that regulate a normal immune response to factor VIII (FVIII). The immune response to FVIII is dependent upon the interaction of different CD4+ T-cell subsets (Th1, Th2 and Th3) specific for FVIII. Failure to activate regulatory CD4+ cells likely plays a crucial role in the development of FVIII inhibitors. Although the basic mechanisms of the immune response to FVIII in the setting of factor replacement therapy are being elucidated, a clear understanding of the relevance of these mechanisms in the context of successful immune tolerance therapy and ultimately gene therapy, awaits further study.
Reding
M T
MT
Division of Hematology, Oncology and Transplantation, Hemophilia and Thrombosis Center, University of Minnesota, Minneapolis, MN, USA. redin002@umn.edu
D019774:Blood Coagulation Factor Inhibitors / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005164:Factor IX / Q000276:immunology* / Q000627:therapeutic use; D005169:Factor VIII / Q000276:immunology* / Q000627:therapeutic use; D006467:Hemophilia A / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
D019774:Blood Coagulation Factor Inhibitors; D005169:Factor VIII; D005164:Factor IX