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Pharmacogenetic testing benefits patients by predicting drug efficacy and risk of adverse drug reactions (ADRs). Pharmacogenetic biomarkers useful in clinical practice include drug-metabolizing enzyme and drug transporter genes and human leukocyte antigen (HLA) genes. HLA genes, which are important molecules involved in human immunity, have long been analyzed for associations with ADRs, such as skin rash, drug-induced liver injury, and agranulocytosis.

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A patient with epilepsy on carbamazepine developed a rapidly progressive cerebellar syndrome. Serial MRI showed progressive posterior fossa T2/fluid attenuated inversion recovery hyperintensity with gadolinium enhancement. Standard cerebrospinal fluid (CSF) analysis was normal.

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Transgenic murine models for the study of drug hypersensitivity reactions linked to HLA-I molecules.

Curr Opin Allergy Clin Immunol

August 2023

Laboratory of Immunology, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration. Silver Spring, Maryland 20993, USA.

Purpose Of Review: Immune-mediated drug hypersensitivity reactions (DHRs) can be life-threatening and an impediment to drug development. Mechanism of disease studies are difficult to perform in humans. Here we review human leukocyte antigens class I (HLA-I) transgenic murine models and highlight how these systems have helped to elucidate drug-specific and host immune factors that initiate, propagate and control severe drug toxicities to skin and liver.

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Adverse drug reactions (ADR) remain the major problems in healthcare. Most severe ADR are unpredictable, dose-independent and termed as type B idiosyncratic reactions. Recent pharmacogenomic studies have demonstrated the strong associations between severe ADR and genetic markers, including specific HLA alleles (e.

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Carbamazepine (CBZ), a widely used antiepileptic drug, is one major cause of the idiosyncratic liver injury along with immune reactions. Conversely, prostaglandin E (PGE2) demonstrates a hepatoprotective effect by regulating immune reactions and promoting liver repair in various types of liver injury. However, the amount of hepatic PGE during CBZ-induced liver injury remains elusive.

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