Plasma Lipid Profiling of Patients with Chronic Ocular Complications Caused by Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

Abstract

Stevens-Johnson syndrome (SJS) and its severe variant, toxic epidermal necrolysis (TEN), are drug-induced acute inflammatory vesiculobullous reactions of the skin and mucous membranes, including the ocular surface. Even after recovery from skin symptoms, some SJS/TEN patients continue to suffer with severe ocular complications (SOCs). Therefore, this study aims to understand the pathophysiology of chronic SOCs. Because plasma lipid profiling has emerged as a useful tool to understand pathophysiological alterations in the body, we performed plasma lipid profiling of 17 patients who suffered from SJS/TEN-associated chronic SOCs. A lipidomics approach yielded 386 lipid molecules and demonstrated that plasma levels of inflammatory oxylipins increased in patients with SJS/TEN-associated chronic SOCs. In addition, oxidized phosphatidylcholines and ether-type diacylglycerols increased in the patients with chronic SOCs, while phosphoglycerolipids decreased. When we compared these lipidomic profiles with those of patients with atopic dermatitis, we found that patients with chronic SOCs, specifically, had decreased levels of ether-type phosphatidylcholines (ePCs) containing arachidonic acid (AA), such as PC(18:0e/20:4) and PC(20:0e/20:4). To confirm our finding, we recruited additional patients, who suffered from SOC associated with SJS/TEN (up to 51 patients), and validated the decreased plasma levels of AA-containing ePCs. Our study provides insight into the alterations of plasma lipidomic profiles in chronic SOCs and into the pathophysiology of SJS/TEN-associated chronic SOCs.

Extracellular Vesicles from Human Plasma Show a Distinctive Proteome and miRNome Profile in Patients with Severe Cutaneous Adverse Reactions

“…The APOA1 gene can be blocked by long noncoding antisense RNAs, and some studies have shown that miRNAs can regulate high density lipoprotein metabolism and reverse cholesterol transport. Recent studies reported an altered lipidic state in patients with SJS/TEN with severe ocular complications characterized by the decrease of ether-type phosphatidylcholine or ePCs, which together with sphingomyelin are two major lipid components of HDL . Our studies further confirm the altered lipidomic state by demonstrating the low expression of the APOA1 which directly correlates with the decrease of the phosphatidylcholine lipids.…”

Disease severity and status in Stevens–Johnson syndrome and toxic epidermal necrolysis: Key knowledge gaps and research needs

“…There have been much fewer studies focusing on biomarkers to monitor severity, progression, and response to therapy during the acute stages of SJS/TEN and how these correlate with long-term morbidity and delayed mortality. Biomarkers that have been studied either singly or in combination in SJS/TEN include procalcitonin ( 32 ); granulysin ( 123 ); IFN-g ( 124 ); interleukin (IL)-8 and granzyme B ( 125 ); endocan, tumor necrosis factor-α, vascular endothelial growth factor, and C-reactive protein; serum IL-17 ( 126 ); complement components ( 127 ); alarmins like the heterodimeric form of S100 calcium-binding protein A8 and S100 calcium-binding protein (A9 S100A8/A9) ( 123 ); chemokines like CXCL9/MIG and CXCL10/IP-10 ( 124 ); antimicrobial peptides like LL-37 ( 128 ); exosomal nucleic acids like miR-375-3p ( 129 ); plasma lipid profiles ( 130 ); renal functions ( 78 , 79 ); neutrophil:lymphocyte ratio; and C-reactive protein:albumin ratio ( 131 ).…”