PDF(Pubmed)
Abstract：
Dapsone and co-trimoxazole are potent antibiotics for treating various infections and inflammations. However, several studies reported the strongly association between severe cutaneous adverse drug reactions (SCARs) to both drugs and the HLA-B*13:01 allele. Rapid and reliable screening for the HLA-B*13:01 allele can mitigate the risk of dapsone-induced SCARs. We developed two methods, multiplex sequence-specific primer PCR (PCR-SSP) and real-time PCR (RT-PCR), tailored for different clinical settings. These methods were optimized to minimize false positives among the Thai population. Clinical validation demonstrated excellent reproducibility, with both methods showing 100 % concordance in repeated tests. PCR-SSP achieved a limit of detection as low as 100 pg of genomic DNA, while RT-PCR reached 1 pg. Overall statistical accuracy was 100.00 % (95 % CI: 98.18 %-100.00 %). Screening for drug-related HLA alleles is crucial for reducing mortality from severe cutaneous adverse drug reactions, especially dapsone hypersensitivity syndrome (DHS) and dapsone-induced hypersensitivity reactions (DIHRs). Our screening approach for dapsone can also be extended to co-trimoxazole, representing a significant advancement in personalized medicine and preemptive pharmacogenetic testing for tailored patient care and safety, albeit further validation in diverse ethnic populations is warranted to ensure universal applicability.
摘要：
氨苯砜和复方新诺明是用于治疗各种感染和炎症的有效抗生素。然而,多项研究报道两种药物的严重皮肤药物不良反应(SCAR)与HLA-B*13:01等位基因密切相关.快速可靠地筛查HLA-B*13:01等位基因可以减轻氨苯砜诱导的SCAR的风险。我们开发了两种方法，多重序列特异性引物PCR(PCR-SSP)和实时PCR(RT-PCR),为不同的临床环境量身定制。对这些方法进行了优化，以最大程度地减少泰国人群中的假阳性。临床验证证明了良好的可重复性，两种方法在重复测试中都显示出100%的一致性。PCR-SSP的检测极限低至100pg的基因组DNA，而RT-PCR达到1μg。总体统计准确度为100.00%(95%CI:98.18%-100.00%)。筛选与药物相关的HLA等位基因对于降低严重皮肤药物不良反应的死亡率至关重要。特别是氨苯砜超敏反应综合征（DHS）和氨苯砜诱导的超敏反应（DIHR）。我们对氨苯砜的筛选方法也可以扩展到复方新诺明，代表了个性化医疗和先发制人的药物遗传测试的显着进步，以实现量身定制的患者护理和安全性，尽管需要在不同种族人群中进一步验证,以确保普遍适用性.
