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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

Sandrine Delignat
1   Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France
2   INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France
3   Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France
,
Julie Rayes
1   Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France
2   INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France
3   Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France
,
Jules Russick
1   Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France
2   INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France
3   Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France
,
Srinivas V. Kaveri
1   Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France
2   INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France
3   Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France
,
Sebastien Lacroix-Desmazes
1   Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France
2   INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France
3   Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France
,
The ABIRISK consortium › Author Affiliations
Further Information

Publication History

Publication Date:
04 June 2018 (online)

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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
 

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