Patients with Naproxen-Induced Liver Injury Display T-cell Memory Responses Towards an Oxidative (S)-O-Desmethyl Naproxen Metabolite but not the Acyl Glucuronide

Thomson, Paul; Fragkas, Nikolaos; Kafu, Laila; Aithal, Guruprasad; Lucena, Maribel; Terracciano, Luigi; Meng, Xiaoli; Pirmohamed, Munir; Brees, Dominique; Kullak-Ublick, Gerd; Odermatt, Alex; Hammond, Thomas; Kammuller, Michael; Naisbitt, Dean

Abstract

Background: Exposure to non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (IBU) and naproxen (NAP) is associated with idiosyncratic drug-induced liver injury (DILI). Carboxylate bioactivation into reactive metabolites (e.g. acyl glucuronides, AG) and resulting T-cell activation is hypothesised as causal for this adverse event. However, conclusive evidence supporting this is lacking. Methods: In this work, we identify CD4+ and CD8+ T-cell hepatic infiltration in a biopsy from an IBU DILI patient. Lymphocyte transformation test and IFN-γ ELIspot,

Citation

Thomson, P., Fragkas, N., Kafu, L., Aithal, G., Lucena, M., Terracciano, L., …Naisbitt, D. (2024). Patients with Naproxen-Induced Liver Injury Display T-cell Memory Responses Towards an Oxidative (S)-O-Desmethyl Naproxen Metabolite but not the Acyl Glucuronide. Allergy, 79(1), 200-214. https://doi.org/10.1111/all.15830

• Journal Article Type: Article
• Acceptance Date: Jun 13, 2023
• Online Publication Date: Jul 29, 2023
• Publication Date: 2024-01
• Deposit Date: Jul 25, 2023
• Publicly Available Date: Jul 29, 2023
• Journal: Allergy
• Print ISSN: 0105-4538
• Electronic ISSN: 1398-9995
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 79
• Issue: 1
• Pages: 200-214
• DOI: https://doi.org/10.1111/all.15830
• Keywords: drug allergy; lymphocytes; clinical immunology
• Public URL: https://nottingham-repository.worktribe.com/output/23475969
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1111/all.15830