Anti-factor VIII antibodies: a 2005 update

Thromb Haemost. 2005 Oct;94(4):760-9. doi: 10.1160/TH05-02-0118.

Abstract

The development of anti-factor VIII (FVIII) antibodies is currently one of the most serious complications in the treatment of haemophilia A patients. Numerous studies in literature report on their epitope specificity, their mechanism of FVIII inactivation, and their relationship with FVIII genetic alterations. During the last two years, however, a particular effort has been made to better understand their generation, with particular emphasis on the interplay of T cells and B cells specific for FVIII and the generation of anti-FVIII antibodies. Moreover, novel strategies to improve the management or treatment of patients with anti-FVIII antibodies have been recently proposed: the use of less immunogenic engineered recombinant FVIII molecules, neutralization of inhibitors by blocking their deleterious activity either by low molecular weight peptide decoys or by anti-idiotypic antibodies, and attempts to suppress the T-cell response involved in the antibody formation. All of these represent promising therapeutic approaches. This review attempts to sum up current knowledge of the nature and properties of anti-FVIII antibodies, their mechanism of action, their neutralization by anti-idiotypic antibodies, and the role of T cells in FVIII inhibitor formation. In the final part, some of the new strategies susceptible to improve the management or the eradication of anti-FVIII antibodies are presented.

Publication types

  • Review

MeSH terms

  • Autoantibodies / immunology*
  • Epitopes / immunology
  • Factor VIII / immunology*
  • Hemophilia A / genetics
  • Hemophilia A / immunology*
  • Humans

Substances

  • Autoantibodies
  • Epitopes
  • Factor VIII