Development of Mucosal PNAd+ and MAdCAM-1+ Venules during Disease Course in Ulcerative Colitis.

Britt Roosenboom,Peter J Wahab,Larissa G.J.M Kemperman,Liselot W Van Erp,Ellen G Van Lochem,Stefan Nierkens,Eelco C Brand,Carolijn Smids,Marcel J.M Groenen,Carmen S Horjus Talabur Horje,Jos Meijer

doi:10.3390/cells9040891

Britt Roosenboom, Peter J Wahab + Show 9 more

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https://doi.org/10.3390/cells9040891

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Journal: Cells	Publication Date: Apr 6, 2020
Citations: 8	License type: CC BY 4.0

Affiliation: Rijnstate Hospital, University Medical Center Utrecht

Abstract

PNAd and MAdCAM-1 addressins on venules are of importance in T-cell homing and potential therapeutic targets in ulcerative colitis (UC). Normally, PNAd+ high endothelial venules (HEVs) are only present in lymphoid organs, whereas small numbers of MAdCAM-1+ venules can be seen in non-lymphoid tissue. We aimed to study their presence in the intestinal mucosa of UC patients at diagnosis and during follow-up, and their correlation with disease activity. Colonic biopsy specimens of 378 UC patients were analyzed by immunohistochemistry for CD3, CD20, ERG, MECA-79 (PNAd) and MECA-376 (MAdCAM-1) and compared to healthy controls (HC). The proportion of PNAd+HEVs in UC at diagnosis was 4.9% (IQR 2.0%–8.3%), while none were detected in HC. During follow-up, PNAd+HEVs completely disappeared in remission (n = 93), whereas the proportion in active disease was similar to baseline (n = 285, p = 0.39). The proportion of MAdCAM-1+venules in UC at baseline was 5.8% (IQR 2.6–10.0). During follow-up, the proportion in remission was comparable to diagnosis, but upregulated (7.5% (IQR 4.4–10.9), p = 0.001) in active disease. In conclusion, PNAd+HEVs appear in UC during active inflammation which could thus serve as a marker for disease activity, whereas MAdCAM-1+venules remain present after inflammation is resolved and increase after subsequent flares, reflecting chronicity and potentially serving as a therapeutic target.

Highlights

Ulcerative colitis (UC) is known to have a heterogenic phenotype reflected by differences in disease location and severity, age of disease onset and response to treatment [1]
In a large cohort of untreated ulcerative colitis (UC) patients at diagnosis we found a high proportion of colonic mucosal peripheral node addressin (PNAd)+ and MAdCAM-1+ venules
In healthy controls (HC), PNAd+ venules were completely absent and MAdCAM-1+ venules were present in very low numbers

Summary

Introduction

Ulcerative colitis (UC) is known to have a heterogenic phenotype reflected by differences in disease location and severity, age of disease onset and response to treatment [1]. The response to treatment differs, suggesting that distinct inflammatory mechanisms drive the course of the disease [2,3,4]. Naive- (Tn ) and central memory T cells (Tcm ) migrate to secondary lymphoid organs (SLOs) by tethering and rolling on specialized cuboidal formed high endothelial venules (HEVs) [5,6]. This process is facilitated through the binding of L-selectin on the surface of. Within SLOs, T cells become activated effector cells (Tem ) and migrate through blood vessels to their site of action, such as the gut mucosa

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