Human leucocyte antigen association of patients with Stevens-Johnson syndrome/toxic epidermal necrolysis with severe ocular complications in Han Chinese
Human leucocyte antigen association of patients with Stevens-Johnson syndrome/toxic epidermal necrolysis with severe ocular complications in Han Chinese
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DOI：
10.1136/bjophthalmol-2020-317105
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发表时间：
2021-01-13
影响因子：
4.1
通讯作者：
Ueta, Mayumi
中科院分区：
文献类型：
--
作者：
Ma, Kevin Sheng-Kai;Chung, Wen Hung;Ueta, Mayumi
背景/目的感冒药（CM）引起的Stevens-Johnson综合征/中毒性表皮坏死松解症（SJS/TEN）可导致严重的眼部并发症（SOC）。本研究的目的是调查人类白细胞抗原（HLA）多态性模式在CM诱导的SJS/TEN发展SOC的患者。方法所有参与者，包括SJS/TEN患者（n=33）和对照组患者（n=98），均通过2016年至2017年的门诊访视入选。通过病历审查或眼部检查诊断SOC（n=26）。使用商业化试剂盒收集患者唾液，并使用PCR检测进行基因分型，然后使用商业珠粒型试剂盒与序列特异性寡核苷酸（SSO）探针（PCR-SSO）杂交。结果SJS/TEN患者中HLA-A*02：07基因携带者频率和基因型频率均显著高于对照组（OR=3.24，95% CI=1.09 ~ 9.60，p=0.049），基因型频率OR=3.89，95% CI=1.49 ~ 10.16，p=0.007）。在具有SOC的CM-SJS/TEN患者中，HLA-A*02：07携带者频率高于对照组（OR=5.56，95%CI =1.52至20.00，p=0.016），等位基因频率也是如此（OR=6.67，95%CI =2.33至20.00，p=0.001）。CM-SJS/TEN患者HLA-B*46：01等位基因频率显著高于对照组（OR=3.85，95%CI =1.52 ~ 10.00，p=0.008）。结论HLA-A*02：07和HLA-B*46：01等位基因与中国汉族CM-SJS/TEN患者SOC显著相关。这些发现表明不同种族之间SJS发病机制的遗传多样性。
Background/aims Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) induced by cold medicine (CM) may result in severe ocular complications (SOCs). The purpose of this study was to investigate the human leucocyte antigen (HLA) polymorphism pattern in CM-induced patients with SJS/TEN developing SOCs. Methods All participants, including patients with SJS/TEN (n=33) and control patients (n=98), were enrolled through visits to the clinic from 2016 to 2017. SOCs were diagnosed (n=26) via a chart review or eye examination. Patient saliva was collected with commercialised kits and genotyped with PCR assays followed by hybridisation with sequence-specific oligonucleotide (SSO) probes (PCR-SSO) using commercial bead-based typing kits. Results In all patients with SJS/TEN with SOCs, the HLA-A*02:07 carrier frequency was significantly higher than that in controls (OR=3.24, 95% CI=1.09 to 9.60, p=0.049), as was the genotype frequency (OR=3.89, 95% CI=1.49 to 10.16, p=0.007). In patients with CM-SJS/TEN with SOCs, the HLA-A*02:07 carrier frequency was higher than that in controls (OR=5.56, 95% CI=1.52 to 20.00, p=0.016), as was the allele frequency (OR=6.67, 95% CI=2.33 to 20.00, p=0.001). In patients with CM-SJS/TEN with SOCs, the HLA-B*46:01 allele frequency was significantly higher than that in controls (OR=3.85, 95% CI=1.52 to 10.00, p=0.008). Conclusions The HLA-A*02:07 and HLA-B*46:01 alleles were significantly associated with SOCs among Han Chinese patients with CM-SJS/TEN. These findings demonstrate the genetic diversity in SJS pathogenesis among different ethnic groups.