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Title: 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.
Austin Authors: Rwandamuriye, Francois X;Chopra, Abha;Konvinse, Katherine C;Choo, Linda;Trubiano, Jason A ;Shaffer, Christian M;Watson, Mark;Mallal, Simon A;Phillips, Elizabeth J
Affiliation: Department of Medicine, University of Melbourne, Parkville, Australia
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee
Divisions of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee
Centre for Antibiotic Allergy and Research, Austin Health, Heidelberg, Victoria, Australia
Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Australia
Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia
Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
Issue Date: Sep-2019 2019-05-31
Publication information: The Journal of molecular diagnostics : JMD 2019; 21(5): 782-789
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.
DOI: 10.1016/j.jmoldx.2019.04.006
ORCID: 0000-0002-5111-6367
PubMed URL: 31158526
Type: Journal Article
Appears in Collections:Journal articles

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