The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Human Leukocyte Antigen (HLA)-B*57:01-Restricted Activation of Drug-Specific T cells Provides the Immunological Basis for Flucloxacillin-Induced Liver Injury
Open accessAbstract
The role of the adaptive immune system in adverse drug reactions that target the liver has not been defined. For flucloxacillin, a delay in the reaction onset and identification of human leukocyte antigen (HLA)-B*57:01 as a susceptibility factor are indicative of an immune pathogenesis. Thus, we characterize flucloxacillin-responsive CD4+ and CD8+ T cells from patients with liver injury and show that naive CD45RA+CD8+ T cells from volunteers expressing HLA-B*57:01 are activated with flucloxacillin when dendritic cells present the drug antigen. T-cell clones expressing CCR4 and CCR9 migrated toward CCL17 and CCL 25, and secreted interferon-gamma (IFN-γ), T helper (Th)2 cytokines, perforin, granzyme B, and FasL following drug stimulation. Flucloxacillin bound covalently to selective lysine residues on albumin in a time-dependent manner and the level of binding correlated directly with the stimulation of clones. Activation of CD8+ clones with flucloxacillin was processing-dependent and restricted by HLA-B*57:01 and the closely related HLA-B*58:01. Clones displayed additional reactivity against β-lactam antibiotics including oxacillin, cloxacillin, and dicloxacillin, but not abacavir or nitroso sulfamethoxazole. Conclusion: This work defines the immune basis for flucloxacillin-induced liver injury and links the genetic association to the iatrogenic disease.
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Cites
Hepatic recruitment of macrophages promotes nonalcoholic steatohepatitis through CCR2
Miura, K., Yang, L., van Rooijen, N., Ohnishi, H., & Seki, E. (2012) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00365.2011 · Cited by 503
Cited by
Andrade, R. J., Chalasani, N., Björnsson, E. S., Suzuki, A., Kullak-Ublick, G. A., Watkins, P. B., Devarbhavi, H., Merz, M., Lucena, M. I., Kaplowitz, N., et al. (2019) · Nature Reviews Disease Primers · doi:10.1038/s41572-019-0105-0 · Cited by 924
Leise, M. D., Poterucha, J. J., & Talwalkar, J. A. (2014) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2013.09.016 · Cited by 356
Nicoletti, P., Aithal, G. P., Bjornsson, E. S., Andrade, R. J., Sawle, A., Arrese, M., Barnhart, H. X., Bondon-Guitton, E., Hayashi, P. H., Bessone, F., et al. (2017) · Gastroenterology · doi:10.1053/j.gastro.2016.12.016 · Cited by 221
Self-citationDrug-induced liver injury: a comprehensive review
Hosack, T., Damry, D., & Biswas, S. (2023) · Therapeutic Advances in Gastroenterology · doi:10.1177/17562848231163410 · Cited by 214
Lauschke, V. M., Shafagh, R. Z., Hendriks, D. F. G., & Ingelman‐Sundberg, M. (2019) · Biotechnology Journal · doi:10.1002/biot.201800347 · Cited by 153
Metadata
- Authors
- Monshi, M. M., Faulkner, L., Gibson, A., Jenkins, R. E., Farrell, J., Earnshaw, C. J., Alfirevic, A., Cederbrant, K., Daly, A. K., French, N., Pirmohamed, M., Park, K. B., & Naisbitt, D. J.
- Venue
- Hepatology
- Published
- 2013-02
- Volume
- 57
- Issue
- 2
- Pages
- 727-739
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2002493942
- Cited by
- 258
- References
- 1
- FWCI
- 11.15
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Human Leukocyte Antigen (HLA)-B*57:01-Restricted Activation of Drug-Specific T cells Provides the Immunological Basis for Flucloxacillin-Induced Liver Injury. https://app.cochat.ai/papers/10.1002/hep.26077
- The paper
- Monshi, M. M., Faulkner, L., Gibson, A., Jenkins, R. E., Farrell, J., Earnshaw, C. J., Alfirevic, A., Cederbrant, K., Daly, A. K., French, N., Pirmohamed, M., Park, K. B., & Naisbitt, D. J. (2013). Human Leukocyte Antigen (HLA)-B*57:01-Restricted Activation of Drug-Specific T cells Provides the Immunological Basis for Flucloxacillin-Induced Liver Injury. Hepatology. https://doi.org/10.1002/hep.26077
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