PMID- 31158526 OWN - NLM STAT- MEDLINE DCOM- 20200701 LR - 20240214 IS - 1943-7811 (Electronic) IS - 1525-1578 (Print) IS - 1525-1578 (Linking) VI - 21 IP - 5 DP - 2019 Sep TI - 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. PG - 782-789 LID - S1525-1578(19)30076-5 [pii] LID - 10.1016/j.jmoldx.2019.04.006 [doi] AB - Human leukocyte antigen (HLA) alleles have been implicated as risk factors for immune-mediated adverse drug reactions. The authors recently reported a strong association between HLA-A*32:01 and vancomycin-induced drug reaction with eosinophilia and systemic symptoms. Identification of individuals with the risk allele before or shortly after the initiation of vancomycin therapy is of great clinical importance to prevent morbidity and mortality, and improve drug safety and antibiotic treatment options. A prerequisite to the success of 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, the authors developed a simple, real-time allele-specific PCR for typing the HLA-A*32:01 allele. Four-hundred and fifty-eight DNA samples including 30 HLA-A*32:01-positive samples were typed by allele-specific PCR. Compared with American Society for Histocompatibility and Immunogenetics-accredited, sequence-based, high-resolution, full-allelic HLA typing, this assay demonstrates 100% accuracy, 100% sensitivity (95% CI, 88.43% to 100%), and 100% specificity (95% CI, 99.14% to 100%). The lowest limit of detection of this assay using PowerUp SYBR Green is 10 ng of template DNA. The assay demonstrates a sensitivity and specificity to differentiate the 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 before or during the course of vancomycin therapy. CI - Copyright (c) 2019 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved. FAU - Rwandamuriye, Francois X AU - Rwandamuriye FX AD - Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia. FAU - Chopra, Abha AU - Chopra A AD - Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia; Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Konvinse, Katherine C AU - Konvinse KC AD - Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Choo, Linda AU - Choo L AD - Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia. FAU - Trubiano, Jason A AU - Trubiano JA AD - Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Infectious Diseases and Centre for Antibiotic Allergy and Research, Austin Health, Heidelberg, Victoria, Australia; Department of Medicine, University of Melbourne, Parkville, Victoria, Australia. FAU - Shaffer, Christian M AU - Shaffer CM AD - Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Watson, Mark AU - Watson M AD - Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia. FAU - Mallal, Simon A AU - Mallal SA AD - Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia; Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Phillips, Elizabeth J AU - Phillips EJ AD - Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address: elizabeth.j.phillips@vanderbilt.edu. LA - eng GR - F30 AI131780/AI/NIAID NIH HHS/United States GR - T32 GM007347/GM/NIGMS NIH HHS/United States GR - P50 GM115305/GM/NIGMS NIH HHS/United States GR - P30 AI110527/AI/NIAID NIH HHS/United States GR - R21 AI139021/AI/NIAID NIH HHS/United States GR - R34 AI136815/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20190531 PL - United States TA - J Mol Diagn JT - The Journal of molecular diagnostics : JMD JID - 100893612 RN - 0 (Anti-Bacterial Agents) RN - 0 (HLA-A Antigens) RN - 6Q205EH1VU (Vancomycin) SB - IM MH - Alleles MH - Anti-Bacterial Agents/*adverse effects MH - Base Sequence MH - Drug Hypersensitivity Syndrome/*diagnosis/etiology/genetics MH - Eosinophilia/chemically induced/*diagnosis/genetics MH - Genetic Testing/*methods MH - HLA-A Antigens/*genetics MH - Humans MH - Polymerase Chain Reaction MH - Sequence Homology MH - Vancomycin/*adverse effects PMC - PMC6734857 EDAT- 2019/06/04 06:00 MHDA- 2020/07/02 06:00 PMCR- 2020/09/01 CRDT- 2019/06/04 06:00 PHST- 2019/02/04 00:00 [received] PHST- 2019/03/13 00:00 [revised] PHST- 2019/04/02 00:00 [accepted] PHST- 2019/06/04 06:00 [pubmed] PHST- 2020/07/02 06:00 [medline] PHST- 2019/06/04 06:00 [entrez] PHST- 2020/09/01 00:00 [pmc-release] AID - S1525-1578(19)30076-5 [pii] AID - 10.1016/j.jmoldx.2019.04.006 [doi] PST - ppublish SO - J Mol Diagn. 2019 Sep;21(5):782-789. doi: 10.1016/j.jmoldx.2019.04.006. Epub 2019 May 31.