Anti-factor VIII antibodies

Géraldine Lavigne-Lissalde; Jean-François Schved; Claude Granier; Sylvie Villard

doi:10.1160/TH05-02-0118

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 94(04): 760-769
DOI: 10.1160/TH05-02-0118

Review Article

Schattauer GmbH

Anti-factor VIII antibodies

A 2005 update

Géraldine Lavigne-Lissalde

¹CNRS UMR 5160, Centre de Pharmacologie et Biotechnologie pour la Santé, Faculté de Pharmacie, Montpellier, France

³Groupe Hospitalo-Universitaire CHU Carremeau, Nîmes, France

,

Jean-François Schved

²Hôpital Universitaire Saint-Eloi, Montpellier, France

,

Claude Granier

¹CNRS UMR 5160, Centre de Pharmacologie et Biotechnologie pour la Santé, Faculté de Pharmacie, Montpellier, France

,

Sylvie Villard

¹CNRS UMR 5160, Centre de Pharmacologie et Biotechnologie pour la Santé, Faculté de Pharmacie, Montpellier, France

› Author Affiliations

Abstract

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

Full Text

References

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