Sun Dan, Yu Chun-Hua, Liu Zhi-Sheng, He Xue-Lian, Hu Jia-Sheng, Wu Ge-Fei, Mao Bing, Wu Shu-Hua, Xiang Hui-Hui
Department of Pediatric Neurology, Wuhan Children's Hospital, Wuhan, 430016, China.
Department of Science Research and Education, Wuhan Children's Hospital, Wuhan, 430016, China.
J Huazhong Univ Sci Technolog Med Sci. 2014 Feb;34(1):146-150. doi: 10.1007/s11596-014-1247-7. Epub 2014 Feb 6.
Previous studies have demonstrated a strong association between carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS) and HLA-B1502 in Han Chinese. Here, we extended the study of HLA-B1502 susceptibility to two different antiepileptic drugs, oxcarbazepine (OXC) and phenobarbital (PB). In addition, we genotyped HLA-B1511 in a case of CBZ-induced SJS with genotype negative for HLA-B1502. The presence of HLA-B1502 was determined using polymerase chain reaction with sequence-specific primers (PCR-SSP). Moreover, we genotyped HLA-B1502 in 17 cases of antiepileptic drugs (AEDs)-induced cutaneous adverse drug reactions (cADRs), in comparison with AEDs-tolerant (n=32) and normal controls (n=38) in the central region of China. The data showed that HLA-B1502 was positive in 5 of 6 cases of AEDs-induced SJS (4 CBZ, 1 OXC and 1 PB), which was significantly more frequent than AEDs-tolerant (2/32, 18 CBZ, 6 PB and 8 OXC) and normal controls (3/38). Compared with AEDs-tolerant and normal controls, the OR for patients carrying the HLA-B1502 with AEDs-induced SJS was 6.25 (95% CI: 1.06-36.74) and 4.86 (95% CI: 1.01-23.47). The sensitivity and specificity of HLA-B1502 for prediction of AEDs-induced SJS were 71.4%. The sensitivity and specificity of HLA-B1502 for prediction of CBZ-induced SJS were 60% and 94%. HLA-B1502 was not found in 11 children with maculopapular exanthema (MPE) (n=9) and hypersensitivity syndrome (HSS) (n=2). However, we also found one case of CBZ-induced SJS who was negative for HLA-B1502 but carried HLA-B1511. It was suggested that the association between the CBZ-induced SJS and HLA-B1502 allele in Han Chinese children can extend to other aromatic AEDs including OXC and PB related SJS. HLA-B1511 may be a risk factor for some patients with CBZ-induced SJS negative for HLA-B1502.
既往研究已证实在中国汉族人群中,卡马西平(CBZ)诱发的史蒂文斯-约翰逊综合征(SJS)与HLA-B1502之间存在强关联。在此,我们将HLA-B1502易感性研究扩展至另外两种不同的抗癫痫药物,奥卡西平(OXC)和苯巴比妥(PB)。此外,我们对1例HLA-B1502基因型阴性的CBZ诱发的SJS患者进行了HLA-B1511基因分型。采用序列特异性引物聚合酶链反应(PCR-SSP)检测HLA-B1502的存在情况。此外,我们对中国中部地区17例抗癫痫药物(AEDs)诱发的皮肤药物不良反应(cADRs)患者进行了HLA-B1502基因分型,并与AEDs耐受者(n = 32)和正常对照者(n = 38)进行比较。数据显示,6例AEDs诱发的SJS患者(4例CBZ、1例OXC和1例PB)中有5例HLA-B1502呈阳性,这一比例显著高于AEDs耐受者(2/32,其中18例CBZ、6例PB和8例OXC)和正常对照者(3/38)。与AEDs耐受者和正常对照者相比,携带HLA-B1502的患者发生AEDs诱发的SJS的比值比(OR)分别为6.25(95%可信区间:1.06 - 36.74)和4.86(95%可信区间:1.01 - 23.47)。HLA-B1502预测AEDs诱发的SJS的敏感性和特异性分别为71.4%。HLA-B1502预测CBZ诱发的SJS的敏感性和特异性分别为60%和94%。在11例斑丘疹(MPE)(n = 9)和超敏综合征(HSS)(n = 2)患儿中未发现HLA-B1502。然而,我们也发现1例CBZ诱发的SJS患者,其HLA-B1502阴性但携带HLA-B1511。提示中国汉族儿童中CBZ诱发的SJS与HLA-B1502等位基因之间的关联可扩展至其他芳香族AEDs,包括OXC和PB相关的SJS。对于一些HLA-B1502阴性的CBZ诱发的SJS患者,HLA-B1511可能是一个危险因素。
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