Repurposing HLA genotype data of renal transplant patients to prevent severe drug hypersensitivity reactions

Lisanne E N Manson; Sander J Delwig; Jos J M Drabbels; Daan J Touw; Aiko P J De Vries; Dave L Roelen; Henk-Jan Guchelaar

doi:10.3389/fgene.2023.1289015

Repurposing HLA genotype data of renal transplant patients to prevent severe drug hypersensitivity reactions

Front Genet. 2023 Oct 16:14:1289015. doi: 10.3389/fgene.2023.1289015. eCollection 2023.

Authors

Lisanne E N Manson^#¹, Sander J Delwig^#¹, Jos J M Drabbels², Daan J Touw³, Aiko P J De Vries^{4

5}, Dave L Roelen^{2

5}, Henk-Jan Guchelaar¹

Affiliations

¹ Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, Netherlands.
² Department of Immunohematology, Leiden University Medical Center, Leiden, Netherlands.
³ Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
⁴ Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, Leiden, Netherlands.
⁵ Leiden Transplant Center, Leiden University Medical Center, Leiden, Netherlands.

^# Contributed equally.

Abstract

Introduction: Specific alleles in human leukocyte antigens (HLAs) are associated with an increased risk of developing drug hypersensitivity reactions induced by abacavir, allopurinol, carbamazepine, oxcarbazepine, phenytoin, lamotrigine, or flucloxacillin. Transplant patients are genotyped for HLA as a routine practice to match a potential donor to a recipient. This study aims to investigate the feasibility and potential impact of repurposing these HLA genotype data from kidney transplant patients to prevent drug hypersensitivity reactions. Methods: A cohort of 1347 kidney transplant recipients has been genotyped in the Leiden University Medical Center (LUMC) using next-generation sequencing (NGS). The risk alleles HLA-A*31:01, HLA-B*15:02, HLA-B*15:11, HLA-B*57:01, and HLA-B*58:01 were retrieved from the NGS data. Medical history, medication use, and allergic reactions were obtained from the patient's medical records. Carrier frequencies found were compared to a LUMC blood donor population. Results: A total of 13.1% of transplant cohort patients carried at least one of the five HLA risk alleles and therefore had an increased risk of drug-induced hypersensitivity for specific drugs. HLA-A*31:01, HLA-B*15:02, HLA-B*57:01, and HLA-B*58:01 were found in carrier frequencies of 4.61%, 1.19%, 4.46%, and 3.35% respectively. No HLA-B*15:11 carrier was found. In total nine HLA-B*57:01 carriers received flucloxacillin and seven HLA-B*58:01 carriers within our cohort received allopurinol. Discussion: Our study shows that repurposing HLA genotype data from transplantation patients for the assignment of HLA risk alleles associated with drug hypersensitivity is feasible. The use of these data by physicians while prescribing drugs or by the pharmacist when dispensing drugs holds the potential to prevent drug hypersensitivity reactions. The utility of this method was highlighted by 13.1% of the transplant cohort patients carrying an actionable HLA allele.

Keywords: HLA; NGS; SCARs; hypersensitivity; kidney transplant patients; pharmacogenetics.

Grants and funding

The authors declare that no financial support was received for the research, authorship, and/or publication of this article.