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P074 Decreased levels of circulating protein S (PROS1) in patients with active Crohn's disease

Sambuelli A.*1, Chavero P.2, de Larrañaga G.3, Errasti A.4, Carrera Silva A.5, Tessone L.6, Peres S.7, Negreira S.2, Gil A.2, Bellicoso M.2, Goncalves S.2, Huernos S.2, Tirado P.2, Rothlin C.8

1Hospital Bonorino Udaondo, IBD Section - Medicine, Buenos Aires, Argentina 2IBD Section - Hospital Bonorino Udaondo, Medicine, Buenos Aires, Argentina 3Hospital of Infectious Diseases F. J. Muñiz, Hemostasis and Thrombosis Laboratory, Buenos, Argentina 4Facultad de Medicina Universidad de Buenos Aires, Instituto de Farmacología, Buenos Aires, Argentina 5Academia Nacional de Medicina, Instituto de Medicina Experimental (IMEX), Buenos Aires, Argentina 6Facultad de Medicina Universidad de Buenos Aires, Hemostasis and Thrombosis Laboratory, Buenos Aires, Argentina 7Hospital of Infectious Diseases F. J. Muñiz, Hemostasis and Thrombosis Laboratory, Buenos Aires, Argentina 8Yale University School of Medicine, Department of Immunobiology, New Haven, United States

Background

Inflammatory bowel diseases (IBD), ulcerative colitis (UC) and CD are associated with an increased risk of thrombosis. Plasma protein S (PROS1) is an anticoagulant that works as a cofactor for activated protein C. PROS1 deficiency increases the risk of thrombosis. Recent pathophysiological and experimental studies in animals showed that PROS1, expressed in T lymphocytes, is also an anti-inflammatory protein playing an inhibitory role in innate immunity due to its agonist activity on tyrosine kinase TAM receptors (TYRO3, AXL and MERTK), Rothlin et al. 2015, Carrera Silva et al. 2013. A decrease in plasma PROS1 could be related to activity or phenotype of human IBD.

Aims: 1. To investigate whether there are differences between PROS1 levels in patients with CD and UC compared to healthy controls. 2. To study whether there is a relationship between PROS1 levels and IBD activity.

Methods

Free PROS1 (immunoturburbimetry, Liatest, Stago, France) was determined in 86 IBD pts.: M 38, F 48 (UC: n 54, CD: n 32) and 30 healthy controls (M 18, F 12), mean ages 38.9±16.0, 40.4±15.0 and 38.2±12.2 respectively. IBD was classified by activity indexes: CDAI (active CD >150), Mayo score (active UC >2), and Montreal classification.

Results

Mean PROS1 levels in CD (91.3±28.5) were significantly lower vs. controls (109.6±23.9, p=0.0077) and UC (104.0±28.2, p=0.048). In active CD (n 20, CDAI: 265.9±68.2) PROS1 levels (85.8±24.3) were significantly lower than in controls (p=0.0015), but vs. CD in remission (n 12: CDAI: 58.2±43.0) did not show significance (100.2±33.5). In active CD, the difference with controls was provided only from the moderate-severe subgroup (n17, CDAI 275.9±69.6, PROS1 84.2±26.0, p=0.0023) but not from other. PROS1 levels were lower in active CD vs. active UC as a trend p=0.082. In active UC (n 31) PROS1 levels (98.90±27.8) were not different from controls or UC in remission (n=23, PROS1 110.91±27.5). The extent of UC (11 proctitis vs. 43 left or extensive) did not show significant differences (116.2±24.9 vs. 100.9±28.5). PROS1 levels in CD were lower, although not significantly in the Small bowel involvement (80.3±15.8) compared with only colon (94.9±31). In CD disease behaviors and perianal disease did not show different levels.

Conclusion

1) PROS1 levels were significantly lower in CD vs. controls and UC. 2) In active CD, PROS 1 levels were different from controls, based on a decrease in the moderate-severe subgroup. Further studies will evaluate the impact of circulating PROS1 decrease in active CD and the activation of TAM receptors. These findings suggest that the decrease of PROS1 in CD could contribute to the increased risk of thrombosis and potentially to the inflammatory process of this disease.