{"doi":"10.1111/tan.14767","title":"A low‐cost, sensitive and specific <scp>PCR</scp>‐based tool for rapid clinical detection of <i>HLA‐B*35</i> alleles associated with delayed drug hypersensitivity reactions","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.","journal":"HLA","year":2022,"id":295664,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":475656,"name":"Pooja Deshpande","orcid":"0000-0002-6037-507X","position":1,"is_corresponding":false},{"id":499245,"name":"Abha Chopra","orcid":"0000-0001-5008-9080","position":2,"is_corresponding":false},{"id":500166,"name":"L. Choo","orcid":null,"position":3,"is_corresponding":false},{"id":237222,"name":"Andrew Gibson","orcid":"0000-0001-9653-3298","position":4,"is_corresponding":false},{"id":106289,"name":"Elizabeth J. Phillips","orcid":"0000-0002-7623-3383","position":5,"is_corresponding":false},{"id":500167,"name":"Yueran Li","orcid":null,"position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T00:31:08.861377Z","pmid":"35968750","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}