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Review
. 2024 Jun 12;23(1):e0218.
doi: 10.1097/CLD.0000000000000218. eCollection 2024 Jan-Jun.

The clinical application of genetic testing in DILI, are we there yet?

Matthew S Krantz  1   2 , Madeline E Marks  2 , Elizabeth J Phillips  2   3   4
Affiliations
Review

The clinical application of genetic testing in DILI, are we there yet?

Matthew S Krantz et al. Clin Liver Dis (Hoboken). .
No abstract available

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Conflict of interest statement

Matthew S. Krantz reports grants from the National Institutes of Health (T32, HL087738-17). Elizabeth J. Phillips reports grants from the National Institutes of Health (R01HG010863, R01AI152183, and U01AI154659) and from the National Health and Medical Research Council of Australia. She receives royalties from and consults for UpToDate. She consults for Janssen, Verve, Biocryst, Ramboll/Esperion, Lexicomp, Regeneron, AstraZeneca, and Novavax.

Figures

FIGURE 1
FIGURE 1
Models of drug-induced HLA-restricted T-cell activation and heterologous immunity. (A) The drug-induced HLA-restricted T-cell activation models include (i) the hapten and pro-hapten model, (ii) HLA and (iii) T-cell receptors (TCR) pharmacological interactions models (PI), and the altered (iv) HLA and (v) TCR peptide models. This model of T-cell activation is not specific to drug-induced liver injury but expected among several mechanisms of T-cell–mediated liver injury, including immune and chemically induced injury. (i) In the hapten/pro-hapten model, an immunogenic drug-modified peptide, created through the binding of drug-antigen to the self-protein, is presented by HLA to the TCR. (ii, iii) The PI models display how T-cell activation occurs by a process of drug-antigen binding with either the risk HLA or TCR. (iv, v) The altered peptide models display how peptides are modified to present as immunogenic to T cells through the binding of drug antigens to HLA and TCR. Reprinted with permission from Deshpande et al (B) The heterologous immunity model. (i) Early-life exposure to a virus leads to (ii) priming of naive T cells with HLA-presented viral peptides. (iii) Future exposure to structurally similar drug antigens (iv) triggers a reactivation of these viral-primed T cells, (v) eliciting an immune-mediated hypersensitivity reaction. Created with BioRender.com. Abbreviations: APC, antigen-presenting cells; HLA, human leukocyte antigens; TCR, T-cell receptors.
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