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Review
. 2021 Oct 25;14(11):1077.
doi: 10.3390/ph14111077.

A Comprehensive Review of HLA and Severe Cutaneous Adverse Drug Reactions: Implication for Clinical Pharmacogenomics and Precision Medicine

Chiraphat Kloypan  1   2 , Napatrupron Koomdee  3   4 , Patompong Satapornpong  5   6 , Therdpong Tempark  7 , Mohitosh Biswas  3   4   8 , Chonlaphat Sukasem  3   4   9   10   11
Affiliations
Review

A Comprehensive Review of HLA and Severe Cutaneous Adverse Drug Reactions: Implication for Clinical Pharmacogenomics and Precision Medicine

Chiraphat Kloypan et al. Pharmaceuticals (Basel). .

Abstract

Human leukocyte antigen (HLA) encoded by the HLA gene is an important modulator for immune responses and drug hypersensitivity reactions as well. Genetic polymorphisms of HLA vary widely at population level and are responsible for developing severe cutaneous adverse drug reactions (SCARs) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), maculopapular exanthema (MPE). The associations of different HLA alleles with the risk of drug induced SJS/TEN, DRESS and MPE are strongly supportive for clinical considerations. Prescribing guidelines generated by different national and international working groups for translation of HLA pharmacogenetics into clinical practice are underway and functional in many countries, including Thailand. Cutting edge genomic technologies may accelerate wider adoption of HLA screening in routine clinical settings. There are great opportunities and several challenges as well for effective implementation of HLA genotyping globally in routine clinical practice for the prevention of drug induced SCARs substantially, enforcing precision medicine initiatives.

Keywords: HLA genetic polymorphisms; SCARs; human leukocyte antigen; pharmacogenomics; precision medicine.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Human leukocyte antigen (HLA) is located on chromosome 6 and structure of HLA class I and class II molecules.
Figure 2
Figure 2
Severe cutaneous adverse drug reactions. (A) indicates Stevens–Johnson syndrome (SJS)/toxic Epidermal necrolysis (TEN), (B) indicates drug reaction with eosinophilia and systemic symptoms (DRESS) and (C) indicates acute generalized exanthematous pustulosis (AGEP).
Figure 3
Figure 3
The mechanisms behind drug-induced delayed hypersensitivity reaction (DHS) are explained in three different theories (a) pharmacological interaction theory (p-i), (b) hapten/prohapten theory, and (c) repertoire alteration theory.
Figure 3
Figure 3
The mechanisms behind drug-induced delayed hypersensitivity reaction (DHS) are explained in three different theories (a) pharmacological interaction theory (p-i), (b) hapten/prohapten theory, and (c) repertoire alteration theory.
Figure 4
Figure 4
Implementation of HLA genotyping in routine clinical practice for optimizing safety of medications. HLA = human leukocyte antigen; HLA-A = HLA-A*31:01, HLA-A*33:03; HLA-B75 = HLA-B*15:02, HLA-B*15:08, HLA-B*15:11, HLA-B*15:21; RT-PCR = real-time polymerase chain reaction; SSO = sequence specific oligonucleotide; SSP = sequence-specific primers; SBT = sequence-based typing; PGx = pharmacogenomics; SJS = Stevens–Johnson syndrome; TEN = toxic epidermal necrolysis; DRESS = drug reaction with eosinophilia and systemic symptoms.
Figure 5
Figure 5
A systematic clinical workflow for implementation of HLA pharmacogenomics into routine clinical practice. HLA = Human leukocyte antigen, PGx = Pharmacogenomics; EMR-Electronic Medical Record, CDSS = Clinical Decision Support System.
Figure 6
Figure 6
The PPM card is a pharmacogenomics identity card (PGx ID card). The QR code will be used to increase the security and confidentiality of the patient’s genetic information. It can be accessed by the pharmacogenetics information of individual patient by private password.
See this image and copyright information in PMC

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