| Autor: |
Roosenboom B; Crohn & Colitis Centre Rijnstate, Department of Gastroenterology and Hepatology, Rijnstate Hospital, 6815 AD Arnhem, The Netherlands., Lochem EGV; Department of Microbiology and Immunology, Rijnstate Hospital, 6815 AD Arnhem, The Netherlands., Meijer J; Department of Pathology, Rijnstate Hospital, 6815 AD Arnhem, The Netherlands., Smids C; Crohn & Colitis Centre Rijnstate, Department of Gastroenterology and Hepatology, Rijnstate Hospital, 6815 AD Arnhem, The Netherlands., Nierkens S; U-DAIR and Center for Translational Immunology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands., Brand EC; Department of Gastroenterology and Hepatology and Center for Translational Immunology, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands., Erp LWV; Crohn & Colitis Centre Rijnstate, Department of Gastroenterology and Hepatology, Rijnstate Hospital, 6815 AD Arnhem, The Netherlands., Kemperman LGJM; Department of Pathology, Rijnstate Hospital, 6815 AD Arnhem, The Netherlands., Groenen MJM; Crohn & Colitis Centre Rijnstate, Department of Gastroenterology and Hepatology, Rijnstate Hospital, 6815 AD Arnhem, The Netherlands., Horje CSHT; Crohn & Colitis Centre Rijnstate, Department of Gastroenterology and Hepatology, Rijnstate Hospital, 6815 AD Arnhem, The Netherlands., Wahab PJ; Crohn & Colitis Centre Rijnstate, Department of Gastroenterology and Hepatology, Rijnstate Hospital, 6815 AD Arnhem, The Netherlands. |
| Abstrakt: |
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. |
