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首页> 外文期刊>Clinical and Translational Allergy >HLA association with antipyretic analgesics-induced Stevens-Johnson Syndrome/toxic epidermal necrolysis with severe ocular surface complications in japanese patients
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HLA association with antipyretic analgesics-induced Stevens-Johnson Syndrome/toxic epidermal necrolysis with severe ocular surface complications in japanese patients

机译：HLA与退热镇痛药引起的史蒂文斯-约翰逊综合症/中毒性表皮坏死合并严重眼表并发症的日本患者

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BackgroundStevens-Johnson syndrome (SJS) and toxic epidermalnecrolysis (TEN), are severe adverse drug reactionswhich are very rare, acute, serious, and potentially fatal.They exhibit characteristic symptoms not only in theskin, but also in the mucosal tissues such as ocular surface,oral cavity, and genitals. Although antipyreticanalgesics (AAs) are some of the most frequent causativedrugs of SJS/TEN, there has been no HLA associationstudies on these drugs-induced SJS/TEN. The scope ofthis study is to investigate HLA-type association withAA-related SJS/TEN with severe ocular surface complications(SOCs).MethodJapanese SJS/TEN patients were recruited to this studythrough the Japan Severe Adverse Reactions (JSAR)research group. The SJS/TEN patients can be divided intothree groups: (i) patients with SOCs who received AA forrelieving a common cold before the onset of SJS/TEN (20cases); (ii) patients without SOCs who received AA forrelieving a common cold before the onset of SJS/TEN (16cases); (iii) patients with SOCs who received causative drug(s) for relieving other than a common cold (38 cases). HLAclass I loci (HLA-A, C, and B) were genotyped for thesepatients and for healthy Japanese volunteers (n = 220). Forthese HLA genotypes, frequencies in the case groups werecompared with those in the healthy controls.ResultsSignificant association of SJS/TEN with HLA-A*02:06 wasfound in the group (i), as previously reported (Ueta et al,Mol Vision 14:550 2008). In addition, we found significantassociation with HLA-A*33:03-C*14:03-B*44:03 haplotypein this group, which is the second most frequent haplotypein Japanese population (5.605%). Fourteen patients of thegroup (i) had been administered acetaminophen, andthese two HLA-type/haplotype associations were still significantin the acetaminophen-administered subgroup ofthe group (i). On the other hand, these two associationswere not significant either in the groups (ii) or (iii),although there was a small difference in the frequencyof HLA-C*14:03-B*44:03 haplotype between groups(i) and (ii).ConclusionIn the Japanese population, we found that HLA-A*02:06genotype and HLA-A*33:03-C*14:03-B*44:03 haplotypeare independently associated with AA-induced SJS/TENwith SOCs. These biomarkers would be useful to discovermechanisms of and to develop a new therapeutic methodfor SOCs caused by AA-induced SJS/TEN.
机译：背景史蒂文斯-约翰逊综合征（SJS）和中毒性表皮坏死溶解（TEN）是严重的药物不良反应，非常罕见，急性，严重甚至可能致命，它们不仅在皮肤中而且在粘膜组织（例如眼表）中均表现出特征性症状，口腔和生殖器。尽管抗热敏镇痛药（AAs）是SJS / TEN的最常见致病性药物，但尚无关于这些药物诱导的SJS / TEN的HLA关联研究。本研究的范围是研究与严重眼表并发症（SOCs）相关的AA相关SJS / TEN的HLA类型。方法通过日本严重不良反应（JSAR）研究组招募日本SJS / TEN患者。 SJS / TEN患者可分为三类：（i）在SJS / TEN发作前接受AA缓解普通感冒的SOC患者（20例）; （ii）在SJS / TEN发作之前接受AA缓解普通感冒而没有SOC的患者（16例）; （iii）因感冒以外的其他原因使用过缓解性药物的SOC患者（38例）。对这些患者和健康的日本志愿者（n = 220）进行了HLA I类位点（HLA-A，C和B）的基因分型。对于这些HLA基因型，将病例组的频率与健康对照组的频率进行比较。结果如先前报道，在（i）组中发现SJS / TEN与HLA-A * 02：06的显着相关性（Ueta等，Mol Vision 14 ：550 2008）。此外，我们发现该组中与HLA-A * 33：03-C * 14：03-B * 44：03单倍型显着相关，这是日本人群中第二常见的单倍型（5.605％）。 （i）组的14位患者接受了对乙酰氨基酚的治疗，而在（i）组对乙酰氨基酚的亚组中，这两个HLA型/单倍型关联仍然很显着。另一方面，尽管两个组之间的HLA-C * 14：03-B * 44：03单倍型的频率差异不大，但在（ii）或（iii）组中这两个关联都不显着。 （ii）结论在日本人群中，我们发现HLA-A * 02：06基因型和HLA-A * 33：03-C * 14：03-B * 44：03单倍型与AA诱导的SJS / TENwith独立相关SOC。这些生物标记物对于发现由AA诱导的SJS / TEN引起的SOC的机制和开发新的治疗方法将是有用的。

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