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Expression patterns of TNFα, MAdCAM1 and STAT3 in intestinal and skin manifestations of inflammatory bowel disease


Vavricka, Stephan R; Galván, Jose A; Dawson, Heather; Soltermann, Alex; Biedermann, Luc; Scharl, Michael; Schoepfer, Alain M; Rogler, Gerhard; Prinz Vavricka, Mareike B; Terracciano, Luigi; Navarini, Alexander A; Zlobec, Inti; Lugli, Alessandro; Greuter, Thomas (2018). Expression patterns of TNFα, MAdCAM1 and STAT3 in intestinal and skin manifestations of inflammatory bowel disease. Journal of Crohn's & Colitis, 12(3):347-354.

Abstract

Background: Pathogenesis of cutaneous extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD) remains elusive. Efficacy of anti-TNF agents suggests TNF-dependent mechanisms. The role of other biologics such as anti-integrins or JAK-inhibitors is not yet clear.
Methods: We performed immunohistochemistry for TNFα, NFκB, STAT1/STAT3, MAdCAM1, CD20/68, caspase 3/9, IFNγ, Hsp-27/70 on 240 intestinal (55 controls, 185 IBD) and 64 skin biopsies (11 controls, 18 Erythema nodosum (EN), 13 Pyoderma gangenosum (PG), 22 psoriasis). A semiquantitative score (0-100%) was used for evaluation.
Results: TNFα was upregulated in intestinal biopsies from active Crohn`s disease (CD) vs. controls (36.2 vs. 12.1, p<0.001), but not ulcerative colitis (UC: 17.9). NFκB however was upregulated in intestinal biopsies from both active CD and UC (43.2 and 34.5 vs. 21.8, p<0.001 and p=0.017). TNFα and NFκB were overexpressed in skin biopsies from EN, PG and psoriasis. No MAdCAM1 overexpression was seen in skin tissues, while it was upregulated in active UC vs. controls (57.5 vs. 35.4, p=0.003). STAT3 was overexpressed in the intestinal mucosa of active and non-active IBD, while a similar upregulation was seen in skin biopsies from EN (84.7 vs. 22.3, p<0.001) and PG (60.5 vs. 22.3, p=0.011), but not in psoriasis. Caspase 3 and CD68 overexpression in skin biopsies distinguished EN/PG from psoriasis and controls.
Conclusions: Upregulation of TNFα/NFκB in EN and PG is compatible with the efficacy of anti-TNF in EIM management. Data on overexpressed STAT3, but not MAdCAM1 support a rationale for JAK-inhibitors in EN and PG, while questioning the role of vedolizumab.

Abstract

Background: Pathogenesis of cutaneous extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD) remains elusive. Efficacy of anti-TNF agents suggests TNF-dependent mechanisms. The role of other biologics such as anti-integrins or JAK-inhibitors is not yet clear.
Methods: We performed immunohistochemistry for TNFα, NFκB, STAT1/STAT3, MAdCAM1, CD20/68, caspase 3/9, IFNγ, Hsp-27/70 on 240 intestinal (55 controls, 185 IBD) and 64 skin biopsies (11 controls, 18 Erythema nodosum (EN), 13 Pyoderma gangenosum (PG), 22 psoriasis). A semiquantitative score (0-100%) was used for evaluation.
Results: TNFα was upregulated in intestinal biopsies from active Crohn`s disease (CD) vs. controls (36.2 vs. 12.1, p<0.001), but not ulcerative colitis (UC: 17.9). NFκB however was upregulated in intestinal biopsies from both active CD and UC (43.2 and 34.5 vs. 21.8, p<0.001 and p=0.017). TNFα and NFκB were overexpressed in skin biopsies from EN, PG and psoriasis. No MAdCAM1 overexpression was seen in skin tissues, while it was upregulated in active UC vs. controls (57.5 vs. 35.4, p=0.003). STAT3 was overexpressed in the intestinal mucosa of active and non-active IBD, while a similar upregulation was seen in skin biopsies from EN (84.7 vs. 22.3, p<0.001) and PG (60.5 vs. 22.3, p=0.011), but not in psoriasis. Caspase 3 and CD68 overexpression in skin biopsies distinguished EN/PG from psoriasis and controls.
Conclusions: Upregulation of TNFα/NFκB in EN and PG is compatible with the efficacy of anti-TNF in EIM management. Data on overexpressed STAT3, but not MAdCAM1 support a rationale for JAK-inhibitors in EN and PG, while questioning the role of vedolizumab.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Gastroenterology and Hepatology
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:JAK-inhibitor, anti-TNF, anti-integrins, extraintestinal manifestations, immunohistochemistry, microarray
Language:English
Date:2018
Deposited On:08 Dec 2017 17:24
Last Modified:01 Mar 2018 02:02
Publisher:Oxford University Press
ISSN:1873-9946
Additional Information:This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Journal of Crohn's and Colitisfollowing peer review. The definitive publisher-authenticated version Stephan R Vavricka, Jose A Galván, Heather Dawson, Alex Soltermann, Luc Biedermann, Michael Scharl, Alain M Schoepfer, Gerhard Rogler, Mareike B Prinz Vavricka, Luigi Terracciano, Alexander Navarini, Inti Zlobec, Alessandro Lugli, Thomas Greuter; Expression Patterns of TNFα, MAdCAM1 and STAT3 in Intestinal and Skin Manifestations of Inflammatory Bowel Disease, Journal of Crohn's and Colitis, jjx158, https://doi.org/10.1093/ecco-jcc/jjx158 is available online at: https://academic.oup.com/ecco-jcc/advance-article-abstract/doi/10.1093/ecco-jcc/jjx158/4647660
OA Status:Hybrid
Publisher DOI:https://doi.org/10.1093/ecco-jcc/jjx158
PubMed ID:29182760

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