Origin and nature of the neutralizing immune response against therapeutic factor VIII

Authors: Bou, Jaoudeh M., Delignat, S., Varthaman, A., and Lacroix-Desmazes, S.

Publication: Med.Sci (Paris); 36,4:341-347.

Affiliations: Centre de recherche des Cordeliers, Inserm, Sorbonne Université, Université de Paris, F-75006, Paris, France.

Abstract: The use of therapeutic proteins induces in some patients the appearance of neutralizing antibodies. This is the case of pro-coagulant factor VIII (FVIII) used in patients with hemophilia A. Several parameters related to the protein itself, to the type of pathology or to the patients, condition the immunogenicity of a therapeutic protein. Understanding these parameters would help to anticipate or prevent the development of neutralizing antibodies. In the case of FVIII, we propose that the development of neutralizing antibodies does not result from an unpredicted immune response but rather from the inability of the patient’s organism to develop an anti-inflammatory or regulatory response.