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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

Li, Y., Deshpande, P., Chopra, A., Choo, L., Gibson, A. and Phillips, E.J. (2022) A low‐cost, sensitive and specific PCR ‐based tool for rapid clinical detection of HLA‐B*35 alleles associated with delayed drug hypersensitivity reactions. HLA .

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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.

Item Type: Journal Article
Murdoch Affiliation(s): Institute for Immunology and Infectious Diseases
Publisher: John Wiley & Sons Ltd
Copyright: © 2022 The Authors.
URI: http://researchrepository.murdoch.edu.au/id/eprint/65927
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