ArticleProceedings of the National Academy of Sciences of the United States of America2012
Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 193 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
193 citing papers in PubMed, 2 syntheses or guidelines pooled it, 416 citations in OpenAlex.
- In Vitro Monitoring of Human T Cell Responses to Skin Sensitizing Chemicals-A Systematic Review.Cells · 2021Pooled it
- HLA-B*39:01:01 is a novel risk factor for antithyroid drug-induced agranulocytosis in Japanese population.The pharmacogenomics journal · 2021Pooled it
- Assessment for Antibodies to Rifapentine and Isoniazid in Persons Developing Flu-Like Reactions During Treatment of Latent Tuberculosis Infection.The Journal of infectious diseases · 2024Trial
- Delayed Drug Hypersensitivity: Mechanistic Advances and Emerging Therapies.Current allergy and asthma reports · 2026Review
- New Insights Into Immunomodulatory Strategies for Drug Hypersensitivity Reactions: An EAACI Task Force Report.Clinical and translational allergy · 2026Review
- Prediction of drug hypersensitivity by comprehensive modeling of HLA-peptidomes.Briefings in bioinformatics · 2026Article
- Omeprazole activation of CD4+ and CD8+ T-cells through off-target covalent modification of cellular proteins.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Delayed-type anaphylactic shock to mannitol: a case report and review of the literature.Journal of medical case reports · 2026Review
- Insights into the Biochemical and Immune Mechanisms in Drug-Induced Liver Injury Pathogenesis.Chemical research in toxicology · 2026Review
- The evolving landscape of pharmacogenomics: Current achievements and future directions.Pharmacological reviews · 2026Review
- Association between HLA alleles and adverse drug reactions. Mechanisms involved.Advances in laboratory medicine · 2026Review
- Co-evolved Partners of Immunity: A Trait-Based Map of Human Keystone Organisms.bioRxiv : the preprint server for biology · 2026Article
- Carbamazepine activates private self and viral reactive TCRs through a drug-permissive HLA-B cleft.Frontiers in immunology · 2026Article
- Human leukocyte antigen pharmacogenetics in infectious diseases: anti-infective drug toxicity and host immune response.Frontiers in pharmacology · 2026Review
- Keystone Epitope Theory: Implications for Hypersensitivity, Autoimmunity, and Transplantation.Pathogens & immunity · 2026Review
- HLA-A*02:01 Presents Penicillin-Modified Cysteinylated Peptides for T Cell Recognition.Allergy · 2025Article
- A review of the immunogenetics of Stevens-Johnson syndrome and toxic epidermal necrolysis.Global medical genetics · 2025Review
- Drug allergy.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2025Review
- Therapeutic Targeting and Structural Characterization of a Sotorasib-Modified KRAS G12C-MHC I Complex Demonstrate the Antitumor Efficacy of Hapten-Based Strategies.Cancer research · 2025Article
- Advancing drug safety in psychiatry: insights from pharmacogenomics of hypersensitivity reactions.Frontiers in pharmacology · 2025Review
133 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
24 authors at 11 institutions in 3 countries.
Funding
Abstract
Idiosyncratic adverse drug reactions are unpredictable, dose-independent and potentially life threatening; this makes them a major factor contributing to the cost and uncertainty of drug development. Clinical data suggest that many such reactions involve immune mechanisms, and genetic association studies have identified strong linkages between drug hypersensitivity reactions to several drugs and specific HLA alleles. One of the strongest such genetic associations found has been for the antiviral drug abacavir, which causes severe adverse reactions exclusively in patients expressing the HLA molecular variant B*57:01. Abacavir adverse reactions were recently shown to be driven by drug-specific activation of cytokine-producing, cytotoxic CD8(+) T cells that required HLA-B*57:01 molecules for their function; however, the mechanism by which abacavir induces this pathologic T-cell response remains unclear. Here we show that abacavir can bind within the F pocket of the peptide-binding groove of HLA-B*57:01, thereby altering its specificity. This provides an explanation for HLA-linked idiosyncratic adverse drug reactions, namely that drugs can alter the repertoire of self-peptides presented to T cells, thus causing the equivalent of an alloreactive T-cell response. Indeed, we identified specific self-peptides that are presented only in the presence of abacavir and that were recognized by T cells of hypersensitive patients. The assays that we have established can be applied to test additional compounds with suspected HLA-linked hypersensitivities in vitro. Where successful, these assays could speed up the discovery and mechanistic understanding of HLA-linked hypersensitivities, and guide the development of safer drugs.
Indexed as
Identifiers
What OpenQuestion holds
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.