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P047. Involvement of PSGL1 and its ligands P-, E- and L-selectins in inflammatory bowel disease (IBD)

A. Pérez-Frías1, M.E. Fernández-Contreras2, R. González-Tajuelo1, P.M. Linares2, M. Guijarro-Rojas3, A. Algaba4, M. Chaparro2, J.P. Gisbert2, A. Urzainqui1, 1Hospital Universitario de La Princesa and IP, Immunology Unit, Madrid, Spain, 2Hospital Universitario de La Princesa, IP and CIBERehd, Gastroenterology Unit, Madrid, Spain, 3Hospital Universitario de La Princesa and IP, Pathology Unit, Madrid, Spain, 4Hospital Universitario de Fuenlabrada, Gastroenterology Unit, Fuenlabrada, Spain

Background

PSGL1 and L-Selectin on leukocytes and P- and E-Selectins on endothelial cells are responsible for the initial steps of leukocyte extravasation to the inflamed tissue. Our group has shown that PSGL1/P-Selectin interaction triggers tolerance signals in human monocyte-derived dendritic cells and that PSGL1 acts as a tolerogenic receptor, essential to maintain the colonic lamina propria homeostasis in mice.

Our aims were: (1) To quantify soluble PSGL1 and its ligands P-, E- and L-selectins in patients with ulcerative colitis (UC) and Crohn's disease (CD), in order to find a characteristic profile of these molecules in inactive and active IBD. (2) To study the expression of PSGL1 in the colonic mucosa of patients with inactive and active UC and CD.

Methods

PSGL1 and P-, E- and L-Selectins levels were measured by ELISA in serum samples from patients with IBD and healthy volunteers. PSGL1 tissue expression was studied by immunohistochemistry in colon biopsies from patients with IBD and patients without immune-mediated diseases as controls. Clinical IBD activity was assessed by the Mayo score for ulcerative colitis (UC), and by the Harvey–Bradshaw index for Crohn's disease (CD). Tissue IBD activity was determined by histological criteria.

Results

48 serum samples were obtained from 16 controls, 22 patients with CD (11 active and 11 inactive) and 10 patients with UC (5 active and 5 inactive). Biopsies were taken from 5 controls, 22 patients with UC (8 inactive and 14 with histological activity) and 7 CD (3 inactive and 4 active). Our preliminary results show that patients with UC have lower serum concentration of PSGL1 and higher levels of P-Selectin than controls, regardless of IBD activity, while L-Selectin is increased in the active disease. Patients with CD have lower concentration of PSGL1 but levels of P-, E- and L-Selectins are not different from controls. Regarding tissue expression, PSGL1 is present in the membrane of colonic mucosa leukocytes from controls and patients with inactive IBD. Membrane pattern disappears as IBD histological activity increases.

Conclusion

Decreased PSGL1 and increased P-Selectin serum levels are associated with UC, regardless of the disease activity, while high levels of L-Selectin are indicative of active UC. CD is associated with lower concentration of PSGL1, without changes in Selectins levels. Membrane PSGL1 expression in colonic mucosa leukocytes is lost as IBD histological activity increases.