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Updated: Dec 22, 2025

Detection of Antibodies That Neutralize the Cellular Uptake of Enzyme Replacement Therapies with a Cell-based Assay
Published on: September 10, 2018
[Origin and nature of the neutralizing immune response against therapeutic factor VIII]
Mélissa Bou Jaoudeh1, Sandrine Delignat1, Aditi Varthaman1
1Centre de recherche des Cordeliers, Inserm, Sorbonne Université, Université de Paris, F-75006, Paris, France.
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.
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.
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