Journal
JOURNAL OF IMMUNOLOGY
Volume 199, Issue 2, Pages 418-424Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1601246
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Funding
- French National Research Agency, Investissements d'Avenir program [ANR10-LABX-53-01]
- European funds (Fonds Europeen de Developpement Regional Grant) [4940 37478]
- Outils Expression et Fonctions du FcRn
- European Union
- European Regional Development Fund
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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-alpha 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-alpha Abs. Wild type and FcRn knockout mice were injected once with either infliximab or adalimumab, alone or preincubated with TNF-alpha. Adalimumab cross-reacts with murine TNF-alpha whereas infliximab is species specific. When injected alone, only adalimumab elicited a humoral response. By preforming immune complexes with TNF-alpha, an anti-infliximab response was elicited. Surprisingly, both wild type and FcRn knockout mice were able to mount an immune response against anti-TNF-alpha Abs, suggesting that immune complexes are a major determinant of this immunization.
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