Applications of immunopharmacogenomics: Predicting, preventing, and understanding immune-mediated adverse drug reactions

Jason H. Karnes; Matthew A. Miller; Katie D. White; Katherine C. Konvinse; Rebecca K. Pavlos; Alec J. Redwood; Jonathan G. Peter; Rannakoe Lehloenya; Simon A. Mallal; Elizabeth J. Phillips

doi:10.1146/annurev-pharmtox-010818-021818

Applications of immunopharmacogenomics: Predicting, preventing, and understanding immune-mediated adverse drug reactions

Jason H. Karnes
, Matthew A. Miller
, Katie D. White
, Katherine C. Konvinse
, Rebecca K. Pavlos
, Alec J. Redwood
, Jonathan G. Peter
, Rannakoe Lehloenya
, Simon A. Mallal
, Elizabeth J. Phillips

Research output: Contribution to journal › Review article › peer-review

53 Scopus citations

Abstract

Adverse drug reactions (ADRs) are a significant health care burden. Immune-mediated adverse drug reactions (IM-ADRs) are responsible for one-fifth of ADRs but contribute a disproportionately high amount of that burden due to their severity. Variation in human leukocyte antigen (HLA) genes has emerged as a potential preprescription screening strategy for the prevention of previously unpredictable IM-ADRs. Immunopharmacogenomics combines the disciplines of immunogenomics and pharmacogenomics and focuses on the effects of immune-specific variation on drug disposition and IM-ADRs. In this review, we present the latest evidence for HLA associations with IM-ADRs, ongoing research into biological mechanisms of IM-ADRs, and the translation of clinical actionable biomarkers for IM-ADRs, with a focus on T cell-mediated ADRs.

Original language	English (US)
Pages (from-to)	463-486
Number of pages	24
Journal	Annual review of pharmacology and toxicology
Volume	59
DOIs	https://doi.org/10.1146/annurev-pharmtox-010818-021818
State	Published - Jan 6 2019

Keywords

Adverse drug reaction
Human leukocyte antigen
Immunopharmacogenomics
Pharmacogenomics
Stevens-Johnson syndrome
Toxic epidermal necrolysis

ASJC Scopus subject areas

Toxicology
Pharmacology

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10.1146/annurev-pharmtox-010818-021818

Cite this

Karnes, J. H., Miller, M. A., White, K. D., Konvinse, K. C., Pavlos, R. K., Redwood, A. J., Peter, J. G., Lehloenya, R., Mallal, S. A., & Phillips, E. J. (2019). Applications of immunopharmacogenomics: Predicting, preventing, and understanding immune-mediated adverse drug reactions. Annual review of pharmacology and toxicology, 59, 463-486. https://doi.org/10.1146/annurev-pharmtox-010818-021818

Karnes, JH, Miller, MA, White, KD, Konvinse, KC, Pavlos, RK, Redwood, AJ, Peter, JG, Lehloenya, R, Mallal, SA & Phillips, EJ 2019, 'Applications of immunopharmacogenomics: Predicting, preventing, and understanding immune-mediated adverse drug reactions', Annual review of pharmacology and toxicology, vol. 59, pp. 463-486. https://doi.org/10.1146/annurev-pharmtox-010818-021818

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abstract = "Adverse drug reactions (ADRs) are a significant health care burden. Immune-mediated adverse drug reactions (IM-ADRs) are responsible for one-fifth of ADRs but contribute a disproportionately high amount of that burden due to their severity. Variation in human leukocyte antigen (HLA) genes has emerged as a potential preprescription screening strategy for the prevention of previously unpredictable IM-ADRs. Immunopharmacogenomics combines the disciplines of immunogenomics and pharmacogenomics and focuses on the effects of immune-specific variation on drug disposition and IM-ADRs. In this review, we present the latest evidence for HLA associations with IM-ADRs, ongoing research into biological mechanisms of IM-ADRs, and the translation of clinical actionable biomarkers for IM-ADRs, with a focus on T cell-mediated ADRs.",

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doi = "10.1146/annurev-pharmtox-010818-021818",

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AU - Pavlos, Rebecca K.

AU - Redwood, Alec J.

AU - Peter, Jonathan G.

AU - Lehloenya, Rannakoe

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KW - Human leukocyte antigen

KW - Immunopharmacogenomics

KW - Pharmacogenomics

KW - Stevens-Johnson syndrome

KW - Toxic epidermal necrolysis

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ER -

Applications of immunopharmacogenomics: Predicting, preventing, and understanding immune-mediated adverse drug reactions

Abstract

Keywords

ASJC Scopus subject areas

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