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Analysis of anti-TNF-induced skin lesions reveals strong Th1 activation with some distinct immunological characteristics


Stoffel, E; Maier, H; Riedl, E; Brüggen, M C; Reininger, B; Schaschinger, M; Bangert, C; Guenova, Emmanuella; Stingl, G; Brunner, P M (2018). Analysis of anti-TNF-induced skin lesions reveals strong Th1 activation with some distinct immunological characteristics. British Journal of Dermatology, 178(5):1151-1162.

Abstract

BACKGROUND: Psoriasiform and eczematous eruptions are the most common dermatological adverse reaction linked to anti-TNF-α therapy. Yet, a detailed characterization of their immune phenotype is lacking.
OBJECTIVES: We sought to characterize anti-TNF-α induced inflammatory skin lesions on a histopathologic, cellular and molecular level, compared to psoriasis, eczema (atopic dermatitis), and healthy control skin.
METHODS: Histopathologic evaluation, gene expression (quantitative RT-PCR) and computer-assisted immunohistologic studies (TissueFAXS) were performed on 19 skin biopsies from IBD (n=17) and rheumatoid arthritis (n=2) patients with new-onset inflammatory skin lesions during anti-TNF-α-therapy.
RESULTS: While most biopsies showed a psoriasiform and/or spongiotic (eczematous) histopathologic architecture, these lesions were inconsistent with either psoriasis or eczema on a molecular level using an established CCL27/iNOS classifier. Despite some differences in immune skewing depending on the specific histopathologic reaction pattern, all anti-TNF-α-induced lesions showed strong IFN-γ activation, at higher levels than in psoriasis or eczema. IFN-γ was most likely produced by CD3/CD4/Tbet-positive Th1 lymphocytes.
CONCLUSIONS: New-onset anti-TNF-α-induced eruptions previously classified as psoriasis or spongiotic dermatitis (eczema) exhibit a molecular profile that is different from either of these disorders. This article is protected by copyright. All rights reserved.

Abstract

BACKGROUND: Psoriasiform and eczematous eruptions are the most common dermatological adverse reaction linked to anti-TNF-α therapy. Yet, a detailed characterization of their immune phenotype is lacking.
OBJECTIVES: We sought to characterize anti-TNF-α induced inflammatory skin lesions on a histopathologic, cellular and molecular level, compared to psoriasis, eczema (atopic dermatitis), and healthy control skin.
METHODS: Histopathologic evaluation, gene expression (quantitative RT-PCR) and computer-assisted immunohistologic studies (TissueFAXS) were performed on 19 skin biopsies from IBD (n=17) and rheumatoid arthritis (n=2) patients with new-onset inflammatory skin lesions during anti-TNF-α-therapy.
RESULTS: While most biopsies showed a psoriasiform and/or spongiotic (eczematous) histopathologic architecture, these lesions were inconsistent with either psoriasis or eczema on a molecular level using an established CCL27/iNOS classifier. Despite some differences in immune skewing depending on the specific histopathologic reaction pattern, all anti-TNF-α-induced lesions showed strong IFN-γ activation, at higher levels than in psoriasis or eczema. IFN-γ was most likely produced by CD3/CD4/Tbet-positive Th1 lymphocytes.
CONCLUSIONS: New-onset anti-TNF-α-induced eruptions previously classified as psoriasis or spongiotic dermatitis (eczema) exhibit a molecular profile that is different from either of these disorders. This article is protected by copyright. All rights reserved.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:TNF-alpha, anti-TNF, eczema, eczematous, psoriasiform, psoriasis
Language:English
Date:2018
Deposited On:21 Dec 2017 13:51
Last Modified:23 May 2018 01:02
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:0007-0963
Additional Information:This is the peer reviewed version of the following article: Stoffel, E., Maier, H., Riedl, E., Brüggen, M.-C., Reininger, B., Schaschinger, M., Bangert, C., Guenova, E., Stingl, G. and Brunner, P.M; Analysis of anti-TNF-induced skin lesions reveals strong Th1 activation with some distinct immunological characteristics. Br J Dermatol. Accepted Author Manuscript, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/bjd.16126/abstract. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-820227.html#terms).
OA Status:Closed
Publisher DOI:https://doi.org/10.1111/bjd.16126
PubMed ID:29143979

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