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Immunological aspects of inhibitor development

M T Reding1

  • 1Division of Hematology, Oncology and Transplantation, Hemophilia and Thrombosis Center, University of Minnesota, Minneapolis, MN, USA. redin002@umn.edu

Haemophilia : the Official Journal of the World Federation of Hemophilia
|November 25, 2006
PubMed

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.

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