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Impact of Adalimumab Treatment on Interleukin-17 and Interleukin-17 Receptor Expression in Skin and Synovium of Psoriatic Arthritis Patients with Mild Psoriasis
Interleukin (IL)-17 and tumor necrosis factor-alpha (TNF)-α are key players in psoriatic arthritis (PsA) pathogenesis. While both cytokines can be therapeutically targeted with beneficial clinical outcome, it is unclear whether inhibiting one cytokine will affect the other at sites of inflammation....
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8869729/ https://www.ncbi.nlm.nih.gov/pubmed/35203534 http://dx.doi.org/10.3390/biomedicines10020324 |
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author | Bolt, Janne W. van Kuijk, Arno W. Teunissen, Marcel B. M. van der Coelen, Dennis Aarrass, Saïda Gerlag, Daniëlle M. Tak, Paul P. van de Sande, Marleen G. Lebre, Maria C. van Baarsen, Lisa G. M. |
author_facet | Bolt, Janne W. van Kuijk, Arno W. Teunissen, Marcel B. M. van der Coelen, Dennis Aarrass, Saïda Gerlag, Daniëlle M. Tak, Paul P. van de Sande, Marleen G. Lebre, Maria C. van Baarsen, Lisa G. M. |
author_sort | Bolt, Janne W. |
collection | PubMed |
description | Interleukin (IL)-17 and tumor necrosis factor-alpha (TNF)-α are key players in psoriatic arthritis (PsA) pathogenesis. While both cytokines can be therapeutically targeted with beneficial clinical outcome, it is unclear whether inhibiting one cytokine will affect the other at sites of inflammation. If both act independently, this might provide a rationale for dual or combined inhibition of both cytokines. Here, we evaluated the effect of TNF blockade in PsA patients on IL-17 levels in both skin and synovial tissue biopsies. PsA patients with mild psoriatic skin lesions were randomized to receive either adalimumab or placebo for four weeks. Synovial and skin biopsies were obtained at weeks zero and four. Skin from healthy donors (HDs) was used for comparison. Expression of IL-17A, IL-17F, IL-17RA and IL-17RC was assessed by immunohistochemistry and analyzed with digital image analysis. We found relatively low levels of IL-17 and its receptors in the skin of PsA patients compared to HD, and only IL-17F in the dermis of lesional psoriatic skin was significantly higher compared to HD skin (p = 0.0002). Histologically IL-17A, IL-17F, IL-17RA and IL-17RC in skin and synovial tissue were not downregulated by adalimumab treatment. Thus, in this cohort of PsA patients with mild psoriasis, TNF blockade did not affect the protein levels of IL-17 cytokines and its receptors in skin and synovium, despite reduced cellular inflammation and improved clinical outcome for joint involvement. |
format | Online Article Text |
id | pubmed-8869729 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88697292022-02-25 Impact of Adalimumab Treatment on Interleukin-17 and Interleukin-17 Receptor Expression in Skin and Synovium of Psoriatic Arthritis Patients with Mild Psoriasis Bolt, Janne W. van Kuijk, Arno W. Teunissen, Marcel B. M. van der Coelen, Dennis Aarrass, Saïda Gerlag, Daniëlle M. Tak, Paul P. van de Sande, Marleen G. Lebre, Maria C. van Baarsen, Lisa G. M. Biomedicines Article Interleukin (IL)-17 and tumor necrosis factor-alpha (TNF)-α are key players in psoriatic arthritis (PsA) pathogenesis. While both cytokines can be therapeutically targeted with beneficial clinical outcome, it is unclear whether inhibiting one cytokine will affect the other at sites of inflammation. If both act independently, this might provide a rationale for dual or combined inhibition of both cytokines. Here, we evaluated the effect of TNF blockade in PsA patients on IL-17 levels in both skin and synovial tissue biopsies. PsA patients with mild psoriatic skin lesions were randomized to receive either adalimumab or placebo for four weeks. Synovial and skin biopsies were obtained at weeks zero and four. Skin from healthy donors (HDs) was used for comparison. Expression of IL-17A, IL-17F, IL-17RA and IL-17RC was assessed by immunohistochemistry and analyzed with digital image analysis. We found relatively low levels of IL-17 and its receptors in the skin of PsA patients compared to HD, and only IL-17F in the dermis of lesional psoriatic skin was significantly higher compared to HD skin (p = 0.0002). Histologically IL-17A, IL-17F, IL-17RA and IL-17RC in skin and synovial tissue were not downregulated by adalimumab treatment. Thus, in this cohort of PsA patients with mild psoriasis, TNF blockade did not affect the protein levels of IL-17 cytokines and its receptors in skin and synovium, despite reduced cellular inflammation and improved clinical outcome for joint involvement. MDPI 2022-01-29 /pmc/articles/PMC8869729/ /pubmed/35203534 http://dx.doi.org/10.3390/biomedicines10020324 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Bolt, Janne W. van Kuijk, Arno W. Teunissen, Marcel B. M. van der Coelen, Dennis Aarrass, Saïda Gerlag, Daniëlle M. Tak, Paul P. van de Sande, Marleen G. Lebre, Maria C. van Baarsen, Lisa G. M. Impact of Adalimumab Treatment on Interleukin-17 and Interleukin-17 Receptor Expression in Skin and Synovium of Psoriatic Arthritis Patients with Mild Psoriasis |
title | Impact of Adalimumab Treatment on Interleukin-17 and Interleukin-17 Receptor Expression in Skin and Synovium of Psoriatic Arthritis Patients with Mild Psoriasis |
title_full | Impact of Adalimumab Treatment on Interleukin-17 and Interleukin-17 Receptor Expression in Skin and Synovium of Psoriatic Arthritis Patients with Mild Psoriasis |
title_fullStr | Impact of Adalimumab Treatment on Interleukin-17 and Interleukin-17 Receptor Expression in Skin and Synovium of Psoriatic Arthritis Patients with Mild Psoriasis |
title_full_unstemmed | Impact of Adalimumab Treatment on Interleukin-17 and Interleukin-17 Receptor Expression in Skin and Synovium of Psoriatic Arthritis Patients with Mild Psoriasis |
title_short | Impact of Adalimumab Treatment on Interleukin-17 and Interleukin-17 Receptor Expression in Skin and Synovium of Psoriatic Arthritis Patients with Mild Psoriasis |
title_sort | impact of adalimumab treatment on interleukin-17 and interleukin-17 receptor expression in skin and synovium of psoriatic arthritis patients with mild psoriasis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8869729/ https://www.ncbi.nlm.nih.gov/pubmed/35203534 http://dx.doi.org/10.3390/biomedicines10020324 |
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