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Alloantibodies to therapeutic factor VIII in hemophilia A: the role of von Willebrand factor in regulating factor VIII immunogenicity
Authors:Johannes Oldenburg  Sébastien Lacroix-Desmazes  David Lillicrap
Affiliation:1.Institute of Experimental Hematology and Transfusion Medicine, University Clinic Bonn, Germany;2.Sorbonne Universités, UPMC Univ Paris 06, INSERM, Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France;3.Department of Pathology and Molecular Medicine, Queen’s University, Kingston, ON, Canada
Abstract:The rising incidence of neutralizing antibodies (inhibitors) against therapeutic factor VIII prompted the conduct of studies to answer the question as to whether this rise is related to the introduction of recombinant factor VIII products. The present article summarizes current opinions and results of non-clinical and clinical studies on the immunogenic potential of recombinant compared to plasma-derived factor VIII concentrates. Numerous studies provided circumstantial evidence that von Willebrand factor, the natural chaperone protein present in plasma-derived factor VIII products, plays an important role in protecting exogenous factor VIII from uptake by antigen presenting cells and from recognition by immune effectors. However, the definite contribution of von Willebrand factor in reducing the inhibitor risk and in the achievement of immune tolerance is still under debate.
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