期刊
BRITISH JOURNAL OF DERMATOLOGY
卷 181, 期 1, 页码 166-174出版社
OXFORD UNIV PRESS
DOI: 10.1111/bjd.17610
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资金
- Medical Research Council grant for the Centre for Drug Safety Science, University of Liverpool [MR/L006758/1]
- MRC [MR/L006758/1] Funding Source: UKRI
Background 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. Objectives 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. Results 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. Conclusions Epidermal HMGB1 expression was decreased in SJS/TEN skin. Retained basal/suprabasal epidermal HMGB1 expression may exacerbate localized injury in SJS/TEN.
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