Diverse expression of TNF-α and CCL27 in serum and blister of Stevens–Johnson syndrome/toxic epidermal necrolysis

Abstract

BackgroundThe pathogenesis of Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) is not fully understood. Our previous study reported that chemokine CCL27 was overexpressed in serum of SJS/TEN patients. The objective of this study was to investigate the levels of CCL27 and TNF-α in serum and blister fluid from patients with SJS/TEN during the acute stage or resolution phase.MethodsA total of 27 patients with SJS/TEN and 39 healthy donors were recruited to the study. Serum and vesicular levels of CCL27 and TNF-α were determined by enzyme-linked immunosorbent assays.ResultsSerum levels of CCL27 and TNF-α were significantly elevated in patients with SJS/TEN during the acute stage as compared to the resolution phase and also compared with levels observed in normal controls (P = 0.001/< 0.001; P = 0.012/< 0.001). Serum TNF-α levels were significantly higher in patients with SJS/TEN during the resolution phase compared with normal controls (P < 0.001). Serum CCL27 levels were positively correlated with TNF-α levels during the acute stage (rs = 0.660; P < 0.001). Blister fluid exhibited much lower CCL27 levels than serum did during the acute stage (P = 0.008). TNF-α levels were much higher in vesicles in contrast to serum from acute stage (P = 0.040) as well as serum from resolution phase (P = 0.029).ConclusionsOur study demonstrated roles of CCL27 and TNF-α in promoting the course of SJS/TEN. CCL27 may act early in the course of disease, via the circulation, whereas TNF-α acts throughout the course of disease, in skin lesions.

Successful treatment of interstitial lung disease related to Stevens–Johnson syndrome/toxic epidermal necrolysis overlap with etanercept: A case report and published work review

“…Although some studies have shown that serum TNF-a levels increase during the progressive stage of SJS/TEN and decrease after treatment with TNF-a inhibitors, 5 our previous study demonstrated that a high level of TNF-a could persist until the resolution stage. 13 Moreover, Berthold et al 14 More interestingly, the TNF-a-IL-6 axis has been demonstrated to be involved in several inflammatory conditions, and TNF-a blockade has been shown to decrease the level of IL-6, 15 which is consistent with our observation. Taken together, the roles of IL-6 and TNF-a in the pathogenetic mechanism underlying ILD associated with SJS/TEN is an exciting area of further inquiry.…”

“…Interestingly, unlike IL‐6, the serum TNF‐α level continued to increase after the initiation of etanercept treatment in our patient. Although some studies have shown that serum TNF‐α levels increase during the progressive stage of SJS/TEN and decrease after treatment with TNF‐α inhibitors, our previous study demonstrated that a high level of TNF‐α could persist until the resolution stage . Moreover, Berthold et al .…”

Current Pharmacogenetic Perspective on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

“…TNF-α can interact with a surface death receptor TNF receptor-1, which will induce the recruitment of adaptor proteins such as FADD to trigger the extrinsic apoptotic pathway, leading to cell death. Plenty of studies support that TNF-α is strongly expressed in SJS/TEN lesions and is involved in the epidermal necrosis ( Caproni et al, 2006 ; Neuman and Nicar, 2007 ; Wang et al, 2018b ). Excitingly, TNF-α antagonists are translated into clinical therapeutics for SJS/TEN in recent years.…”

Metabolic Phenotypes in Asthmatic Adults: Relationship with Inflammatory and Clinical Phenotypes and Prognostic Implications

“…“Phenotypes” are external manifestations of asthma that result from the combination of hereditary and environmental influences [ 3 , 7 , 68 ], and which may occur in varying combinations [ 5 , 69 , 70 ] and even concurrently [ 71 ]. Furthermore, asthma phenotypes are not associated with a specific underlying pathophysiological mechanism, since different mechanisms may lead to the same phenotypic features, particularly in clinical terms [ 5 , 68 , 69 , 70 , 72 ].…”