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A rapid allele-specific assay for HLA-A*32:01 to identify patients at risk for vancomycin-induced Drug Reaction with Eosinophilia and systemic symptoms

Rwandamuriye, F.X., Chopra, A., Konvinse, K.C., Choo, L., Trubiano, J.A., Shaffer, C.M., Watson, M., Mallal, S.A. and Phillips, E.J. (2019) A rapid allele-specific assay for HLA-A*32:01 to identify patients at risk for vancomycin-induced Drug Reaction with Eosinophilia and systemic symptoms. The Journal of Molecular Diagnostics, 21 (5). pp. 782-789.

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Embargoed until April 2020.

Link to Published Version: https://doi.org/10.1016/j.jmoldx.2019.04.006
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Abstract

Human leukocyte antigen (HLA) alleles have been implicated as risk factors for immune-mediated adverse drug reactions. We recently reported a strong association between HLA-A*32:01 and vancomycin-induced drug reaction with eosinophilia and systemic symptoms (DRESS). Identification of individuals with the risk allele prior to or shortly after the initiation of vancomycin therapy is of great clinical importance to prevent morbidity and mortality, improve drug safety and antibiotic treatment options. A prerequisite to the success of a pharmacogenetic screening tests is the development of simple, robust, cost-effective single HLA allele test that can be implemented in routine diagnostic laboratories. In this study, we developed a simple, real-time allele-specific PCR for typing the HLA-A*32:01 allele. Four-hundred and fifty-eight DNA samples including thirty HLA-A*32:01-positive samples were typed by allele-specific PCR. Compared to ASHI accredited sequence-based high-resolution, full allelic HLA typing, this assay demonstrates 100% accuracy, sensitivity of 100% (95% CI: 88.43% to 100%) and specificity of 100% (95% CI: 99.14% to 100%). The lowest limit of detection of this assay using the Power Up SYBR Green is 10 ng of template DNA. The assay demonstrates a sensitivity and specificity to differentiate HLA-A*32:01 allele from closely related non-HLA-A*32 alleles and may be used in clinical settings to identify individuals with the risk allele prior or during the course of vancomycin therapy…

Item Type: Journal Article
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Publisher: Elsevier Inc.
Copyright: © 2019 Elsevier Inc. on behalf of the American Society for Investigative Pathology and the Association for Molecular Pathology
URI: http://researchrepository.murdoch.edu.au/id/eprint/46324
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