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The association between the number of HLA risk alleles and drug allergy and its implications for HLA screening – a case-control study

The Pharmacogenomics Journal volume 25, Article number: 1 (2025) Cite this article

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Abstract

Patients carrying specific HLA risk alleles are at higher risk for developing drug hypersensitivity reactions, yet pre-therapeutic screening is uncommon. We examined whether patients with a history of drug allergies have more HLA risk alleles to assess whether these patients are potential candidates for pre-therapeutic HLA screening. We performed a case-control study with patients who had a self-reported history of drug allergy (N = 94) and patients without such a history (N = 185). HLA regions were sequenced by use of Alloseq Tx for HLA-A -B, -C, -DP, -DQ and -DR genotypes. A logistic regression was performed to investigate whether the number of HLA risk alleles differed between cases and controls. Sequencing data of 279 patients were available for this analysis. There was no statistically significant difference in the mean number of unique HLA risk alleles between the cases and controls (5.31 vs 5.31, p = 0.9397). Therefore, patients with a self-reported history of drug allergy do not form a suitable group for pre-therapeutic screening for HLA risk alleles to prevent future drug allergies.

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Data availability

The datasets generated during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, Netherlands

    Lisanne E. N. Manson, Jesse J. Swen & Henk-Jan Guchelaar

  2. Department of Immunohematology, Leiden University Medical Center, Leiden, Netherlands

    Jacqueline D. H. Anholts, Jos J. M. Drabbels & Dave L. Roelen

  3. Leiden Transplant Center, Leiden University Medical Center, Leiden, The Netherlands

    Dave L. Roelen

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  1. Lisanne E. N. Manson
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  2. Jacqueline D. H. Anholts
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  3. Jos J. M. Drabbels
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  4. Jesse J. Swen
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  6. Henk-Jan Guchelaar
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Contributions

LENM, JJS, and HJG designed the study. LENM wrote the manuscript and performed the data analysis. JDHA and JJMD performed the genotyping. DLR, JJS and HJG critically revised the manuscript.

Corresponding author

Correspondence to Henk-Jan Guchelaar.

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The authors declare no competing interests.

Ethics approval and consent to participate

The trial was done in accordance with the principles of the Declaration of Helsinki. The Medical Ethics Committee Leiden The Hague Delft (METC LDD) has given a declaration of no objection for the conduction of this study. All patients have provided written informed consent before taking part in this study. This study was registered in the Dutch Trial Register (NTR) under ID NL-OMON21376.

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Manson, L.E.N., Anholts, J.D.H., Drabbels, J.J.M. et al. The association between the number of HLA risk alleles and drug allergy and its implications for HLA screening – a case-control study. Pharmacogenomics J 25, 1 (2025). https://doi.org/10.1038/s41397-025-00362-5

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