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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

Background

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.

Methods

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.

Results

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 (r = +0.7 p = 0.001). No extrafollicular PNAd+ HEVs were detected in biopsies of patients in remission during follow-up (n = 57 median 0.0: IQR 0.0–0.0). In active disease (n = 53), PNAd expressing HEVs were not significant different from baseline numbers (median 4.2: IQR 1.6–7.6, p = 0.178). Patients nonresponding to 5ASA induction therapy after initial diagnosis had significant higher baseline percentages of PNAd expressing ERG+ vessels (p = 0.046) in colonic biopsies compared with responding patients. Median percentage of MAdCAM expressing ERG+ vessels at baseline was 5.5% (IQR 2.6–10.1). During follow-up in both active disease and remission, significant elevation was demonstrated for MAdCAM expression on ERG+ vessels (resp. 7.5%(IQR 3.3–12.5), p = 0.028 and 8.8%(IQR 4.9–13.8), p = 0.022).

Conclusion

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.