-
Views
-
Cite
Cite
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, Volume 12, Issue 3, March 2018, Pages 347–354, https://doi.org/10.1093/ecco-jcc/jjx158
Close - Share Icon Share
Abstract
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.
We performed immunohistochemistry for TNFα, NFκB, STAT1/STAT3, MAdCAM1, CD20/68, caspase 3/9, IFNγ, and 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.
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, respectively]. TNFα and NFκB were overexpressed in skin biopsies from EN, PG, and psoriasis. No MAdCAM1 overexpression was seen in skin tissues, whereas 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, and 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.
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.
- tumor necrosis factors
- immunohistochemistry
- integrins
- inflammatory bowel disease
- cd20 antigens
- biological products
- erythema nodosum
- intestines
- psoriasis
- pyoderma gangrenosum
- skin manifestations
- up-regulation (physiology)
- skin
- skin biopsies
- cd68 antigen, human
- protein overexpression
- tumor necrosis factor inhibitors
- stat3 protein
- janus kinase inhibitors
- stat1 gene
- caspase-3
- intestinal biopsy
- vedolizumab
