Laboratory of Cyto-Molecular Genetics, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.
Cornea, Cataract & Refractive Surgery Services, Dr. R P Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
Mol Vis. 2022 Dec 31;28:526-535. eCollection 2022.
This study sought to investigate the association of molecular markers with chronic ocular sequelae in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).
One hundred SJS/TEN patients (200 eyes) with confirmed diagnosis were enrolled between July 2011 and July 2015 from a tertiary eye-care hospital, and their clinical histories were noted. Each eye was scored for severity of manifestation on a scale of 0-5. Peripheral blood samples were collected for DNA followed by screening for interleukin (IL-4, IL-13, IL-4R) polymorphisms, HLA-A locus allele typing, and sera to detect levels of the apoptotic markers granulysin and sFas L.
Of the 100 enrolled patients (53 males/47 females; age range: 6-58 years), the incriminating drugs were non-steroidal anti-inflammatory (52%), antibiotics (10%), sulphonamides (8%), anti-epileptics (6%), and unknown (24%). Significant differences in the frequencies of IL-4R polymorphism, HLA-A3301, HLA-A02, and HLA-A*2402 alleles, and elevated levels of granulysin and sFas L were observed in patients compared to controls. The ocular complications of conjunctival keratinization (p=0.004) showed an association with IL-13 promoter region (IL-13a) genotypes.
The study highlights the possible association of interleukin-13 with severity-graded chronic sequelae and the role of HLA-A alleles- HLA-A3301, HLA-A02, and HLA-A*2402 in SJS/TEN causation and manifestation. Screening of these alleles may help caregivers to identify markers associated with severe and lifelong ocular complications, and help in appropriate treatment and management of the condition.
本研究旨在探讨分子标志物与史蒂文斯-约翰逊综合征/中毒性表皮坏死松解症（SJS/TEN）慢性眼部后遗症的关系。
2011 年 7 月至 2015 年 7 月，我们从一家三级眼科医院招募了 100 名确诊的 SJS/TEN 患者（200 只眼），并记录了他们的临床病史。每只眼的表现严重程度均按 0-5 分进行评分。采集外周血样进行 DNA 检测，然后筛选白细胞介素（IL-4、IL-13、IL-4R）多态性、HLA-A 基因座等位基因分型和血清以检测凋亡标志物颗粒溶素和 sFasL 的水平。
在纳入的 100 名患者（53 名男性/47 名女性；年龄范围：6-58 岁）中，致病药物分别是非甾体类抗炎药（52%）、抗生素（10%）、磺胺类药物（8%）、抗癫痫药（6%）和未知（24%）。与对照组相比，IL-4R 多态性、HLA-A3301、HLA-A02 和 HLA-A*2402 等位基因以及颗粒溶素和 sFasL 水平升高的频率在患者中存在显著差异。结膜角化（p=0.004）的眼部并发症与白细胞介素-13 启动子区域（IL-13a）基因型有关。
本研究强调了白细胞介素-13 可能与慢性后遗症的严重程度分级有关，以及 HLA-A 等位基因-HLA-A3301、HLA-A02 和 HLA-A*2402 在 SJS/TEN 发病机制和表现中的作用。对这些等位基因的筛查可以帮助护理人员识别与严重和终身眼部并发症相关的标志物，并有助于对病情进行适当的治疗和管理。
