The Role of NLRP3 Inflammasome in the Pathogenesis of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis.

Abstract

Stevens Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) are mainly drug-induced severe cutaneous adverse reactions with increased mortality. It also involves the eyes causing ocular surface disease leading to visual impairment and blindness. The role of NLRP3 Inflammasome in causing ocular surface disease and keratinocyte apoptosis is not fully explored. This study is focused on determining the role of NLRP3 Inflammasome in the pathogenesis of Stevens Johnson Syndrome/Toxic Epidermal Necrolysis. The NLRP3 Inflammasome plays a crucial role in the pathogenesis of Stevens Johnson Syndrome/Toxic Epidermal Necrolysis and may correlate with the degree of severity of skin detachment and ocular surface disease. This study looked at the expression of the NLRP3 Inflammasome in the skin of patients with biopsy confirm Stevens Johnson Syndrome/Toxic Epidermal Necrolysis compared to the lichen planus and normal controls by immunohistochemistry as well as observing the mitochondrial function of platelets challenged with plasma from patients with Stevens Johnson Syndrome/Toxic Epidermal Necrolysis and Normal Human Plasma using Agilent Seahorse XF Analyzer. Under a current, Loyola IRB approved protocol, 12 collected and archived unstained slides of skin and blood plasma samples from patients with biopsy confirmed Stevens Johnson Syndrome/Toxic Epidermal Necrolysis was used for this study. Immunohistochemical analysis was performed using anti-NLRP3 antibodies followed by imaging on a Delta Vision microscope. The precise roles of cytokines and chemokine receptors in severity of skin detachment has not been completely studied. The identification of the roles of NLRP3 in Stevens Johnson Syndrome/Toxic Epidermal Necrolysis would bridge the gaps in the basic understanding regarding the pathogenesis of this disease spectrum. NLRP3 Inflammasome is a potential therapeutic target and its inhibition by phytochemicals may be appropriate effective treatment strategies in the management of this condition.