Inhibitor Formation in Congenital Hemophilia A: an Immunological Perspective

Sandrine Delignat; Julie Rayes; Jules Russick; Srinivas V. Kaveri; Sebastien Lacroix-Desmazes; The ABIRISK consortium

doi:10.1055/s-0038-1657777

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2018; 44(06): 517-530
DOI: 10.1055/s-0038-1657777

Review Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Inhibitor Formation in Congenital Hemophilia A: an Immunological Perspective

Authors

Sandrine Delignat

¹Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France

²INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France

³Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France
Julie Rayes

¹Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France

²INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France

³Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France
Jules Russick

¹Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France

²INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France

³Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France
Srinivas V. Kaveri

¹Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France

²INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France

³Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France
Sebastien Lacroix-Desmazes

¹Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France

²INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France

³Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France

The ABIRISK consortium

Abstract

The immunogenicity of therapeutic factor VIII (FVIII) in patients with hemophilia A has been puzzling scientific and clinical communities for more than 3 decades. Indeed, the development of inhibitory antibodies to FVIII remains a major clinical challenge and is associated with enormous societal costs. Thus, the reasons for which a presumably innocuous, short-lived, intravenously administered glycoprotein triggers such a deleterious, long-lasting neutralizing immune response is an enigma. This review does not pretend to bring an answer to this challenging question. It will however summarize the latest findings regarding the molecular interactions at play in the recognition of FVIII by the immune cells, the validity of the proposed risk factors for FVIII alloimmunization, and the different solutions that allow induction of FVIII-specific tolerance in preclinical models of hemophilia A.

Keywords

hemophilia A - factor VIII - immunogenicity

Full Text

References

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