Alterations in serum and intestinal ACE2 in Inflammatory Bowel Disease and the impact of inflammation

Fiona Jones^1,2*Ciara Egan¹Miriam Tosetto¹Moritz Strowitzki²Sarah J. Kierans²Catherine Rowan¹Margaret Walshe¹Elizabeth J Ryan³Juliette Sheridan¹Garret Cullen¹Hugh Mulcahy¹Sean Martin¹Maura Cotter¹Cormac Taylor²Glen A Doherty^1,2

• ¹St. Vincent's University Hospital, Dublin, Ireland
• ²School of Medicine, College of Health and Agricultural Sciences, University College Dublin, Dublin, Ireland
• ³Department of Biological Sciences, University of Limerick, Limerick, Ireland

Background/Aims ACE2 is highly expressed in the gut and with known alterations in expression in IBD patients potentially linked to gut inflammation and fibrosis. In addition, little is known about the role of serum soluble ACE2 (sACE2) or its hypothetical role in SARS-CoV-2 binding. We sought to evaluate tissue and serum ACE2 profiles in IBD and healthy controls and evaluate alterations related to disease activity and medical therapy. Methods Circulating sACE2 and intestinal tissue ACE2 was evaluated respectively in serum samples and endoscopic biopsies from patients with IBD and healthy controls in addition to murine DSS induced colitis. Results 91 IBD (UC/ n=41; CD n=50) and 55 controls were analysed. Immunohistochemical ACE2 staining in controls was limited to brush border expression with markedly increased colonic ACE2 expression (and reduced ileal ACE2 expression) in IBD. This was not observed in the mouse model which demonstrated positive ileal ACE2 and negative colonic staining in healthy and DSS mice. Colonic ACE2 staining was further increased in Ulcerative Colitis in inflammation (% staining, 20(5-30) vs. 5(0-6.5), p<0.015) and in IBD patients receiving corticosteroids (% staining, 20(20-40) vs 10(0-20), p<0.052). Steroid use was associated with significantly lower sACE2 with a trend towards reduced sACE2 with biologic exposure. Conclusion We observe significant increases in colonic ACE2 expression in IBD, especially with active colitis. Corticosteroids further modify the observed imbalance between tissue and serum ACE2 levels.