A low‐cost, sensitive and specific PCR ‐based tool for rapid clinical detection of HLA‐B*35 alleles associated with delayed drug hypersensitivity reactions

Y. Li; P. Deshpande; A. Chopra; L. Choo; A. Gibson; E.J. Phillips

doi:10.1111/tan.14767

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A low‐cost, sensitive and specific PCR ‐based tool for rapid clinical detection of HLA‐B*35 alleles associated with delayed drug hypersensitivity reactions

Journal article

Open access

Peer reviewed

A low‐cost, sensitive and specific PCR ‐based tool for rapid clinical detection of HLA‐B*35 alleles associated with delayed drug hypersensitivity reactions

Y. Li, P. Deshpande, A. Chopra, L. Choo, A. Gibson and E.J. Phillips

HLA, Vol.100(6), pp.610-616

2022

DOI: https://doi.org/10.1111/tan.14767

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Abstract

HLA (HLA) alleles are risk factors for CD8+ T-cell-mediated drug hypersensitivity reactions. However, as most HLA associations are incompletely predictive and/or involve risk alleles at low frequency, costly sequence-based typing can elude an economically productive cost: benefit ratio for clinical validation studies and diagnostic and/or preventative screening. Hence rapid and low-cost detection assays are now required, both for single alleles but also across risk loci associated with broader multi-disease risk; exemplified by associations with diverse alleles in HLA-B*35, including HLA-B*35:01 and green tea- or co-trimoxazole-induced liver injury. Here, we developed a cost-effective (<$10USD) qPCR assay for rapid (<2.5 h) clinical detection of HLA-B*35 alleles. The assay was validated using 430 DNA samples with previous American society for histocompatibility and immunogenetics-accredited sequence-based high-resolution HLA typing, positively detecting all HLA-B*35 allelic variants in our cohort, and as expected by primer design, the six samples that expressed low-frequency B*78:01. The assay did not result in positive detection for any negative control allele. With expected detection of B*35 and B*78, our assay sensitivity (95% CI, 95.07%–100.00%) and specificity (95% CI, 98.97%–100.00%) of 100% using as low as 10 ng of DNA provides a reliable HLA-B*35 screening tool for clinical validation and HLA–risk-based prevention and diagnostics.

Details

Title: A low‐cost, sensitive and specific PCR ‐based tool for rapid clinical detection of HLA‐B*35 alleles associated with delayed drug hypersensitivity reactions
Authors/Creators: Y. Li (Author/Creator) - Murdoch University
P. Deshpande (Author/Creator) - Murdoch University
A. Chopra (Author/Creator) - Murdoch University
L. Choo (Author/Creator) - Murdoch University
A. Gibson (Author/Creator) - Murdoch University
E.J. Phillips (Author/Creator) - Murdoch University, Research and Innovation Office
Publication Details: HLA, Vol.100(6), pp.610-616
Publisher: John Wiley & Sons Ltd
Identifiers: 991005544044007891
Murdoch Affiliation: Research and Innovation Office; Institute for Immunology and Infectious Diseases; Personalised Medicine Centre
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.265 Dermatology - Skin Allergies; 1.265.1140 Drug Hypersensitivity
Web Of Science research areas: Cell Biology; Immunology; Pathology
ESI research areas: Molecular Biology & Genetics