P015 PNAd+ and MAdCAM+ high endothelial venules correlate with disease activity in ulcerative colitis
B. Roosenboom*1, P. Wahab1, J. Meijer2, C. Smids1, M. Groenen1, E. Van Lochem3, C. Horjus Talabur Horje1
1Rijnstate Crohn and Colitis Centre, Gastroenterology and Hepatology, Arnhem, The Netherlands, 2Rijnstate Hospital, Department of Pathology, Arnhem, The Netherlands, 3Rijnstate Hospital, Department of Microbiology and Immunology, Arnhem, The Netherlands
Tertiary lymphoid organs (TLOs) comprising peripheral node addressin positive (PNAd+) and/or MAdCAM+ high endothelial venules (HEVs) have been found to play an important role in local immunological dysregulation in chronic immune-mediated disorders and malignancies. Their presence have a predictive value for disease course and response to therapy. Identification of these HEVs in the early phase of ulcerative colitis (UC) might help stratify patients to enable personalised medicine. We aimed to investigate the presence of these HEVs at UC diagnosis and their development during follow-up. Furthermore, we studied their association with disease activity and response to therapy.
Retrospectively collected colonic biopsy specimens from 110 UC patients at first presentation and during follow-up were analysed by immunohistochemistry after determining the Geboes score. Immunostaining was performed using antibodies: MECA-79 (anti-PNAd), MECA-367 (anti-MAdCAM), ERG (endothelial cells), CD3 (T cells) and CD20 (B-cells). The expression of extrafollicular PNAd+ on all vessels (ERG) was correlated to disease activity, disease course and response to therapy.
In total, 110 newly diagnosed UC patients were analysed. Percentages of PNAd expressing ERG+ vessels at baseline ranged from 0.0% to 29.8% (median 5.4; IQR 1.9–10.3). Higher numbers of extrafollicular PNAd+HEVs were associated with higher numbers of colonic lymphoid follicles (
Formation of extrafollicular PNAd+HEVs was present in active disease while absent in remission. High numbers of PNAd+HEVs were associated with no response to 5ASA induction therapy and with more colonic follicles, suggesting TLO formation. MAdCAM expression increased during disease course independent of disease activity.