Pioneering Research to Elucidate the Pathogenic Mechanism and Genetic Susceptibility of Stevens Johnson Syndrome/Toxic Epidermal Necrolysis

本研究的目的是进行全基因组联合研究，以更详细地阐明伴有严重眼表并发症的Stevens Johnson综合征/中毒性表皮坏死松解症(SJS/TEN)的病理生理机制。我们的研究发现前列腺素E受体3(EP3)的6个单核苷酸多态(SNPs)(rs17131450、rs5702、rs1325949、rs7543182、rs7555874和rs4147114)与SJS/TEN显著相关。SJS/TEN严重眼表并发症患者结膜上皮细胞中EP3的表达未见EP3蛋白表达。另一方面，EP3蛋白在结膜松弛或翼状胬肉对照组的结膜上皮细胞中呈阳性表达。此外，我们还在PTGER3-TLR3和人类白细胞抗原-A*0206-TLR3基因座对中发现了一个具有SJS遗传易感性的变量。

The purpose of this present study was to perform a Genome-Wide Association Study (GWAS) in order to elucidate in greater detail the pathophysiology of Stevens Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) with severe ocular surface complications. Our GWAS findings revealed 6 single-nucleotide polymorphisms (SNPs) (rs17131450, rs5702, rs1325949, rs7543182, rs7555874, and rs4147114) in prostaglandin E receptor 3 (EP3) that are significantly associated with SJS/TEN. When we looked for the expression of EP3 in the conjunctival epithelium of SJS/TEN patients with severe ocular surface complications, we did not find EP3 protein. On the other hand, the EP3 protein was present in the conjunctival epithelium of the control patients with conjunctivochalasis or pterygium. Moreover, we found a variable with SJS genetic susceptibility effects involved in the locus-pairs of genes PTGER3-TLR3 and HLA-A*0206-TLR3.