Necroptosis in SJS/TEN: RIPK1 and RIPK3 Expression and Implications for Disease Pathogenesis 2259694

Abstract Introduction Stevens—Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN) are rare, potentially life-threatening skin conditions, often triggered by medications. They inflict damage on various epithelial and mucosal surfaces, including but not limited to the eyes, lungs, and GI tract. The pathogenesis of SJS/TEN is still unknown, however, several studies have concluded that necroptosis, a type of cell death pathway, is likely involved. Targeting the molecular players of necroptosis, such as RIPK1 and RIPK3, could offer therapeutic benefits in the treatment of these severe disorders. This study expands on previous work from our lab, which demonstrated through immunohistochemistry that there is significant expression of RIPK3 in SJS/TEN biopsy samples. Methods The study examined the expression levels of RIPK1 and RIPK3 in skin biopsies from patients with biopsy- confirmed SJS/TEN, using lichen planus as a positive control and normal skin as a baseline control. Immunohistochemistry was employed for this analysis. Additionally, the circulating levels of RIPK1 and RIPK3 in the plasma of SJS/TEN patients, mixed pathology patients for positive controls, and normal human plasma for baseline controls was measured using quantitative ELISA kits. Results Increased expression of RIPK1 and RIPK3 was noted in SJS/TEN skin biopsy and plasma samples when compared to both positive and baseline controls. Conclusion These findings strengthen the evidence that necroptosis plays a role in the pathogenesis of SJS/TEN and highlights the involvement of RIPK1 and RIPK3 as key inflammatory mediators, as well as, targets for therapeutic intervention. Funding Source Illinois Society for the Prevention of Blindness (ISPB) Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)