Serum and blister-fluid elevation and decreased epidermal content of high-mobility group box 1 protein in drug-induced Stevens-Johnson syndrome/toxic epidermal necrolysis

Carr, DF, Wang, C-W, Bellon, T, Ressel, L ORCID: 0000-0002-6614-1223, Nwikue, G, Shrivastava, V, Bergfeld, W, Jorgensen, AL ORCID: 0000-0002-6977-9337, Chung, W-H and Pirmohamed, M ORCID: 0000-0002-7534-7266 (2019) Serum and blister-fluid elevation and decreased epidermal content of high-mobility group box 1 protein in drug-induced Stevens-Johnson syndrome/toxic epidermal necrolysis. BRITISH JOURNAL OF DERMATOLOGY, 181 (1). pp. 166-174.

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Abstract

<h4>Background</h4>High-mobility group box 1 (HMGB1) is a damage-associated molecular-pattern protein. Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are serious, immune-mediated skin-blistering conditions.<h4>Objectives</h4>To determine serum and/or blister-fluid total HMGB1 levels in SJS/TEN cohorts, and HMGB1 expression in formalin-fixed, paraffin-embedded (FFPE) SJS/TEN skin vs. healthy and maculopapular exanthema (MPE) skin. Methods Serum HMGB1 was quantified in Malawian nevirapine-induced hypersensitivity, Taiwanese SJS/TEN and Spanish SJS/TEN cohorts. FFPE skin (healthy skin, MPE, SJS/TEN) was stained and assessed for HMGB1 expression.<h4>Results</h4>Serum total HMGB1 was not significantly elevated in patients with nevirapine-induced SJS/TEN (3·98 ± 2·17 ng mL^-1 ), MPE (3·92 ± 2·75 ng mL^-1 ) or drug reaction with eosinophilia and systemic symptoms (4·73 ± 3·00 ng mL^-1 ) vs. tolerant controls (2·97 ± 3·00 ng mL^-1 ). HMGB1 was significantly elevated in Taiwanese patients with SJS/TEN, highest during the acute phase (32·6 ± 26·6 ng mL^-1 ) vs. the maximal (19·7 ± 23·2 ng mL^-1 ; P = 0·007) and recovery (24·6 ± 25·3 ng mL^-1 ; P = 0·027) phases. In blister fluid from Spanish patients with SJS/TEN, HMGB1 (486·8 ± 687·9 ng mL^-1 ) was significantly higher than in serum (8·8 ± 7·6 ng mL^-1 ; P <0·001). Preblistered SJS/TEN skin showed decreased epidermal nuclear HMGB1 expression in upper epidermis vs. healthy or MPE skin but retained basal/suprabasal expression.<h4>Conclusions</h4>Epidermal HMGB1 expression was decreased in SJS/TEN skin. Retained basal/suprabasal epidermal HMGB1 expression may exacerbate localized injury in SJS/TEN.

Item Type:	Article
Uncontrolled Keywords:	Epidermis, Humans, Stevens-Johnson Syndrome, Blister, HMGB1 Protein, Biopsy, Prospective Studies, Adult, Aged, Middle Aged, Female, Male, Young Adult, Biomarkers
Depositing User:	Symplectic Admin
Date Deposited:	07 Jan 2019 10:47
Last Modified:	19 Jan 2023 01:08
DOI:	10.1111/bjd.17610
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3030798