Crucial Role for Immune Complexes but Not FcRn in Immunization against Anti–TNF-α Antibodies after a Single Injection in Mice - Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 Accéder directement au contenu
Article Dans Une Revue Journal of Immunology Année : 2017

Crucial Role for Immune Complexes but Not FcRn in Immunization against Anti–TNF-α Antibodies after a Single Injection in Mice

Christophe Arnoult

Résumé

The immunogenicity of infliximab and adalimumab is a major concern because patients may develop Abs also called antidrug Abs (ADA), directed against these anti–TNF-α Abs after just a few weeks of treatment. These ADAs can lead to a decrease in biologic concentration, which is associated with lower treatment efficacy. Our aim was to study the involvement of immune complexes and neonatal Fc receptor (FcRn) in the emergence of ADAs in the case of anti–TNF-α Abs. Wild type and FcRn knockout mice were injected once with either infliximab or adalimumab, alone or preincubated with TNF-α. Adalimumab cross-reacts with murine TNF-α whereas infliximab is species specific. When injected alone, only adalimumab elicited a humoral response. By preforming immune complexes with TNF-α, an anti-infliximab response was elicited. Surprisingly, both wild type and FcRn knockout mice were able to mount an immune response against anti–TNF-α Abs, suggesting that immune complexes are a major determinant of this immunization.

Domaines

Immunologie
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Dates et versions

hal-02019721 , version 1 (14-02-2019)

Identifiants

Citer

Christophe Arnoult, Guillaume Brachet, Diana Cadena Castaneda, Nicolas Azzopardi, Christophe Passot, et al.. Crucial Role for Immune Complexes but Not FcRn in Immunization against Anti–TNF-α Antibodies after a Single Injection in Mice. Journal of Immunology, 2017, 199 (2), pp.418-424. ⟨10.4049/jimmunol.1601246⟩. ⟨hal-02019721⟩
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