Development of Mucosal PNAd<sup>+</sup> and MAdCAM-1<sup>+</sup> Venules during Disease Course in Ulcerative Colitis
Britt Roosenboom,
Ellen G. van Lochem,
Jos Meijer,
Carolijn Smids,
Stefan Nierkens,
Eelco C. Brand,
Liselot W. van Erp,
Larissa G.J.M. Kemperman,
Marcel J.M. Groenen,
Carmen S. Horjus Talabur Horje,
Peter J. Wahab
Affiliations
Britt Roosenboom
Crohn & Colitis Centre Rijnstate, Department of Gastroenterology and Hepatology, Rijnstate Hospital, 6815 AD Arnhem, The Netherlands
Ellen G. van Lochem
Department of Microbiology and Immunology, Rijnstate Hospital, 6815 AD Arnhem, The Netherlands
Jos Meijer
Department of Pathology, Rijnstate Hospital, 6815 AD Arnhem, The Netherlands
Carolijn Smids
Crohn & Colitis Centre Rijnstate, Department of Gastroenterology and Hepatology, Rijnstate Hospital, 6815 AD Arnhem, The Netherlands
Stefan Nierkens
U-DAIR and Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
Eelco C. Brand
Department of Gastroenterology and Hepatology and Center for Translational Immunology, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands
Liselot W. van Erp
Crohn & Colitis Centre Rijnstate, Department of Gastroenterology and Hepatology, Rijnstate Hospital, 6815 AD Arnhem, The Netherlands
Larissa G.J.M. Kemperman
Department of Pathology, Rijnstate Hospital, 6815 AD Arnhem, The Netherlands
Marcel J.M. Groenen
Crohn & Colitis Centre Rijnstate, Department of Gastroenterology and Hepatology, Rijnstate Hospital, 6815 AD Arnhem, The Netherlands
Carmen S. Horjus Talabur Horje
Crohn & Colitis Centre Rijnstate, Department of Gastroenterology and Hepatology, Rijnstate Hospital, 6815 AD Arnhem, The Netherlands
Peter J. Wahab
Crohn & Colitis Centre Rijnstate, Department of Gastroenterology and Hepatology, Rijnstate Hospital, 6815 AD Arnhem, The Netherlands
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.
