{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T04:53:30Z","timestamp":1692766410204},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T00:00:00Z","timestamp":1661472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1123499"],"award-info":[{"award-number":["APP1123499"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50GM115305","R01AI152183","R01HG010863","R21AI139021","U01AI154659"],"award-info":[{"award-number":["P50GM115305","R01AI152183","R01HG010863","R21AI139021","U01AI154659"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HLA"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:p>HLA (HLA) alleles are risk factors for CD8+ T\u2010cell\u2010mediated drug hypersensitivity reactions. However, as most HLA associations are incompletely predictive and\/or involve risk alleles at low frequency, costly sequence\u2010based typing can elude an economically productive cost: benefit ratio for clinical validation studies and diagnostic and\/or preventative screening. Hence rapid and low\u2010cost detection assays are now required, both for single alleles but also across risk loci associated with broader multi\u2010disease risk; exemplified by associations with diverse alleles in HLA\u2010B*35, including <jats:italic>HLA\u2010B<\/jats:italic>*<jats:italic>35<\/jats:italic>:<jats:italic>01<\/jats:italic> and green tea\u2010 or co\u2010trimoxazole\u2010induced liver injury. Here, we developed a cost\u2010effective (&lt;$10USD) qPCR assay for rapid (&lt;2.5\u00a0h) clinical detection of <jats:italic>HLA\u2010B<\/jats:italic>*<jats:italic>35<\/jats:italic> alleles. The assay was validated using 430 DNA samples with previous American society for histocompatibility and immunogenetics\u2010accredited sequence\u2010based high\u2010resolution HLA typing, positively detecting all <jats:italic>HLA\u2010B<\/jats:italic>*<jats:italic>35<\/jats:italic> allelic variants in our cohort, and as expected by primer design, the six samples that expressed low\u2010frequency <jats:italic>B<\/jats:italic>*<jats:italic>78<\/jats:italic>:<jats:italic>01<\/jats:italic>. The assay did not result in positive detection for any negative control allele. With expected detection of <jats:italic>B<\/jats:italic>*<jats:italic>35<\/jats:italic> and <jats:italic>B<\/jats:italic>*<jats:italic>78<\/jats:italic>, our assay sensitivity (95% CI, 95.07%\u2013100.00%) and specificity (95% CI, 98.97%\u2013100.00%) of 100% using as low as 10\u00a0ng of DNA provides a reliable <jats:italic>HLA\u2010B<\/jats:italic>*<jats:italic>35<\/jats:italic> screening tool for clinical validation and HLA\u2013risk\u2010based prevention and diagnostics.<\/jats:p>","DOI":"10.1111\/tan.14767","type":"journal-article","created":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T09:23:15Z","timestamp":1660555395000},"page":"610-616","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A low\u2010cost, sensitive and specific <scp>PCR<\/scp>\u2010based tool for rapid clinical detection of <i>HLA\u2010B*35<\/i> alleles associated with delayed drug hypersensitivity reactions"],"prefix":"10.1111","volume":"100","author":[{"given":"Yueran","family":"Li","sequence":"first","affiliation":[{"name":"Institute for Immunology and Infectious Diseases (IIID) Murdoch University  Perth Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pooja","family":"Deshpande","sequence":"additional","affiliation":[{"name":"Institute for Immunology and Infectious Diseases (IIID) Murdoch University  Perth Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abha","family":"Chopra","sequence":"additional","affiliation":[{"name":"Institute for Immunology and Infectious Diseases (IIID) Murdoch University  Perth Australia"},{"name":"Department of Medicine Vanderbilt University Medical Centre  Nashville Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Choo","sequence":"additional","affiliation":[{"name":"Institute for Immunology and Infectious Diseases (IIID) Murdoch University  Perth Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Gibson","sequence":"additional","affiliation":[{"name":"Institute for Immunology and Infectious Diseases (IIID) Murdoch University  Perth Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth J.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Institute for Immunology and Infectious Diseases (IIID) Murdoch University  Perth Australia"},{"name":"Department of Medicine Vanderbilt University Medical Centre  Nashville Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,8,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0706135"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2217\/14622416.9.10.1543"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102133.2012.10894.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0000000000000078"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13765"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000441280"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119505"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.08.007"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.13430"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-74588-6_195"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1089-3261(05)70097-0"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)07873-X"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742\u20107843.2012.00868.x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kex253"},{"issue":"4","key":"e_1_2_9_16_1","first-page":"1152","article-title":"Genome\u2010wide association study of nevirapine hypersensitivity in a sub\u2010Saharan African HIV\u2010infected population","volume":"72","author":"Carr DF","year":"2017","journal-title":"J Antimicrob 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