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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
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 c...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617791/ https://www.ncbi.nlm.nih.gov/pubmed/30613954 http://dx.doi.org/10.1111/bjd.17610 |
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author | Carr, D.F. Wang, C.‐W. Bellón, T. Ressel, L. Nwikue, G. Shrivastava, V. Bergfeld, W. Jorgensen, A.L. Chung, W.‐H. Pirmohamed, M. |
author_facet | Carr, D.F. Wang, C.‐W. Bellón, T. Ressel, L. Nwikue, G. Shrivastava, V. Bergfeld, W. Jorgensen, A.L. Chung, W.‐H. Pirmohamed, M. |
author_sort | Carr, D.F. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6617791 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-66177912019-07-22 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, D.F. Wang, C.‐W. Bellón, T. Ressel, L. Nwikue, G. Shrivastava, V. Bergfeld, W. Jorgensen, A.L. Chung, W.‐H. Pirmohamed, M. Br J Dermatol Original Articles 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. John Wiley and Sons Inc. 2019-03-26 2019-07 /pmc/articles/PMC6617791/ /pubmed/30613954 http://dx.doi.org/10.1111/bjd.17610 Text en © 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Carr, D.F. Wang, C.‐W. Bellón, T. Ressel, L. Nwikue, G. Shrivastava, V. Bergfeld, W. Jorgensen, A.L. Chung, W.‐H. Pirmohamed, M. 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 |
title | 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
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title_full | 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
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title_fullStr | 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
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title_full_unstemmed | 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
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title_short | 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
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title_sort | 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 |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617791/ https://www.ncbi.nlm.nih.gov/pubmed/30613954 http://dx.doi.org/10.1111/bjd.17610 |
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