ArticleThe Journal of clinical investigation2018
A transgenic mouse model for HLA-B*57:01-linked abacavir drug tolerance and reactivity.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 60 citations in OpenAlex.
- Risk Assessment in Drug Hypersensitivity: Detecting Small Molecules Which Outsmart the Immune System.Frontiers in allergy · 2022Pooled it
- Associations between human leukocyte antigen polymorphisms and hypersensitivity to antiretroviral therapy in patients with human immunodeficiency virus: a meta-analysis.BMC infectious diseases · 2019Pooled it
- Combined immune modulation reveals carbamazepine-associated CD8Archives of toxicology · 2026Article
- Article
- JAK inhibition may prevent drug hypersensitivity reactions.JCI insight · 2026Article
- Carbamazepine activates private self and viral reactive TCRs through a drug-permissive HLA-B cleft.Frontiers in immunology · 2026Article
- Keystone Epitope Theory: Implications for Hypersensitivity, Autoimmunity, and Transplantation.Pathogens & immunity · 2026Review
- Neuronal FGF13 Inhibits Mitochondria-Derived Damage Signals to Prevent Neuroinflammation and Neurodegeneration in a Mouse Model of Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Updates in the pathogenesis of SJS/TEN.Allergology international : official journal of the Japanese Society of Allergology · 2025Review
- TSC22 domain family member 3 links natural killer cells to CD8+ T cell-mediated drug hypersensitivity.Signal transduction and targeted therapy · 2025Article
- Insights into regulatory T-cell and type-I interferon roles in determining abacavir-induced hypersensitivity or immune tolerance.Frontiers in immunology · 2025Article
- Exploring recent advances in drugs severe cutaneous adverse reactions immunopathology.Allergy · 2025Review
- Pathological changes in various organs in HLA-B*57:01 transgenic mice with abacavir-induced skin eruption.Toxicological research · 2024Article
- Development of mouse models with restricted HLA-B∗57:01 presentation for the study of flucloxacillin-driven T-cell activation and tolerance in liver injury.The Journal of allergy and clinical immunology · 2023Article
- HIV-Associated Immune Dysregulation in the Skin: A Crucible for Exaggerated Inflammation and Hypersensitivity.The Journal of investigative dermatology · 2023Review
- Updates on the immunopathology and genomics of severe cutaneous adverse drug reactions.The Journal of allergy and clinical immunology · 2023Review
- Skin infiltrating T-cell profile of drug reaction with eosinophilia and systemic symptoms (DRESS) reactions among HIV-infected patients.Frontiers in medicine · 2023Article
- Article
- Abacavir inhibits but does not cause self-reactivity to HLA-B*57:01-restricted EBV specific T cell receptors.Communications biology · 2022Article
- The important role of non-covalent drug-protein interactions in drug hypersensitivity reactions.Allergy · 2022Review
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Adverse drug reactions (ADRs) are a major obstacle to drug development, and some of these, including hypersensitivity reactions to the HIV reverse transcriptase inhibitor abacavir (ABC), are associated with HLA alleles, particularly HLA-B*57:01. However, not all HLA-B*57:01+ patients develop ADRs, suggesting that in addition to the HLA genetic risk, other factors may influence the outcome of the response to the drug. To study HLA-linked ADRs in vivo, we generated HLA-B*57:01-Tg mice and show that, although ABC activated Tg mouse CD8+ T cells in vitro in a HLA-B*57:01-dependent manner, the drug was tolerated in vivo. In immunocompetent Tg animals, ABC induced CD8+ T cells with an anergy-like phenotype that did not lead to ADRs. In contrast, in vivo depletion of CD4+ T cells prior to ABC administration enhanced DC maturation to induce systemic ABC-reactive CD8+ T cells with an effector-like and skin-homing phenotype along with CD8+ infiltration and inflammation in drug-sensitized skin. B7 costimulatory molecule blockade prevented CD8+ T cell activation. These Tg mice provide a model for ABC tolerance and for the generation of HLA-B*57:01-restricted, ABC-reactive CD8+ T cells dependent on both HLA genetic risk and immunoregulatory host factors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.