APHIA Poster Presentation Asia-Pacific Histocompatibility and Immunogenetics Association Meeting 2023

HLA Alleles, Drug Hypersensitivity Reactions and Drug Efficacy (#110)

Venkat Doddi 1 , Alicia Crisafio 1 , Alison Castley 1 , Rod Williams 1 , Virunyar Youngyuen 1 , Laila Gizzarelli 1 , Jonathan Downing 1 , Lloyd D'Orsogna 1
  1. Clinical Immunology, Pathwest, Perth, Western Australia, Australia

Drug hypersensitivity reactions are clinically diverse reactions that occur when T lymphocytes recognise fragments of a drug compound as foreign, triggering an adverse immune reaction. In most cases, these reactions are mild but in extreme cases it can lead to anaphylactic shock. Many drugs that are known to elicit an adverse immune response, have an association to the human leukocyte antigen (HLA) region of the major histocompatibility complex (MHC). HLA alleles associated with drug hypersensitivity reactions include the association of HLA-B*57:01 to Abacavir, HLA-A*31:01 and B*15:02 to Carbamazepine. These alleles are associated with specific ethnic populations. Antibiotics are also a growing drug class, having the potential to elicit a hypersensitivity response associated to HLA, eg. HLA-A*32 associated with a Vancomycin hypersensitivity. Uveal melanoma is the most common intraocular cancer, which is treated by Tebentafusp and is only effective for patients with the HLA-A*02:01 allele. Therefore, there is a requirement to obtain a patient’s HLA typing result in a timely manner, prior to administering treatment.

Pathwest Immunology department uses the single locus HLA-A and -B HISTOSPOT® hybridisation assay to obtain a patient’s HLA typing results. From January 2022 to May 2023, a total of 135 requests for drug hypersensitivity testing were received. 

From those, 25/135 (18.5%) requests had the associated HLA allele. Specifically, 7 of 47 Carbamazepine requests had the HLA-B*15:02 and/or HLA-A*31:01 associated alleles, and 12 of 52 requested for Abacavir had the HLA-B*57:01 allele present. None of the 5 Flucloxacillin requests had the associated B*57:01 allele. Of the Allopurinol requests, 4/24 had the HLA-B*58:01 allele present and 1 of 6 Vancomycin requests had the HLA-A*32:01 allele. The single request for uveal melanoma had the required HLA-A*02:01 allele for drug treatment.

Drug hypersensitivity requests are reported to prevent adverse drug hypersensitivity reactions in patients and provide treatment options for patients.