Expression Patterns of TNFα, MAdCAM1 and STAT3 in Intestinal and Skin Manifestations of Inflammatory Bowel Disease.

Vavricka, Stephan R; Galván Hernández, José Alberto; Dawson, Heather; Soltermann, Alex; Biedermann, Luc; Scharl, Michael; Schoepfer, Alain M; Rogler, Gerhard; Prinz Vavricka, Mareike B; Terracciano, Luigi; Navarini, Alexander; 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), pp. 347-354. Elsevier 10.1093/ecco-jcc/jjx158

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Translational Research Unit
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology

UniBE Contributor:

Galván Hernández, José Alberto; Dawson, Heather; Zlobec, Inti and Lugli, Alessandro

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1873-9946

Publisher:

Elsevier

Language:

English

Submitter:

Inti Zlobec

Date Deposited:

31 Jan 2018 16:14

Last Modified:

07 Mar 2018 01:32

Publisher DOI:

10.1093/ecco-jcc/jjx158

PubMed ID:

29182760

Uncontrolled Keywords:

JAK-inhibitor anti-TNF anti-integrins extraintestinal manifestations immunohistochemistry microarray

BORIS DOI:

10.7892/boris.110619

URI:

https://boris.unibe.ch/id/eprint/110619

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