Ma Kevin Sheng-Kai, Chung Wen Hung, Hsueh Yi-Jen, Chen Shin-Yi, Tokunaga Katsushi, Kinoshita Shigeru, Ma David H K, Ueta Mayumi
Department of Life Science, National Taiwan University, Taipei, Taiwan.
Limbal Stem Cell Laboratory, Department of Ophthalmology, Chang Gung Memorial Hospital Linkou Main Branch, Taoyuan, Taiwan.
Br J Ophthalmol. 2022 May;106(5):610-615. doi: 10.1136/bjophthalmol-2020-317105. Epub 2021 Jan 13.
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.
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.
In all patients with SJS/TEN with SOCs, the HLA-A02:07 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-A02:07 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).
The HLA-A02:07 and HLA-B46:01 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.
背景/目的:感冒药(CM)诱发的史蒂文斯-约翰逊综合征/中毒性表皮坏死松解症(SJS/TEN)可能导致严重眼部并发症(SOCs)。本研究旨在调查CM诱发的SJS/TEN并发SOCs患者的人类白细胞抗原(HLA)多态性模式。
所有参与者,包括SJS/TEN患者(n = 33)和对照患者(n = 98),于2016年至2017年通过门诊就诊纳入研究。通过病历回顾或眼科检查诊断出SOCs患者(n = 26)。使用商业化试剂盒收集患者唾液,并用PCR检测进行基因分型,随后使用商业化基于微珠的分型试剂盒与序列特异性寡核苷酸(SSO)探针杂交(PCR-SSO)。
在所有并发SOCs的SJS/TEN患者中,HLA-A02:07携带者频率显著高于对照组(OR = 3.24,95%CI = 1.09至9.60,p = 0.049),基因型频率也是如此(OR = 3.89,95%CI = 1.49至10.16,p = 0.007)。在并发SOCs的CM-SJS/TEN患者中,HLA-A02:07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)。在并发SOCs的CM-SJS/TEN患者中,HLA-B*46:01等位基因频率显著高于对照组(OR = 3.85,95%CI = 1.52至10.00,p = 0.008)。
在汉族CM-SJS/TEN患者中,HLA-A02:07和HLA-B46:01等位基因与SOCs显著相关。这些发现证明了不同种族SJS发病机制中的遗传多样性。