Summary
The development of anti-factorVIII (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.
Keywords
Coagulation inhibitors - Factor VIII - haemophilia A