Levels of the anticoagulant and anti-inflammatory protein S (PROS1) in patients with inflammatory bowel disease (IBD) relationship with disease activity, IBD disease patterns, and C4-binding protein (C4BP)

A. SAMBUELLI; P. CHAVERO; G. DE LARRAÑAGA; A. ERRASTI; S. PERES; L. TESSONE; S. NEGREIRA; N. SILVIA; M. BELLICOSO; S. HUERNOS ; S. GONCALVES; P. TIRADO; E.A. CARRERA SILVA; C. ROTHLIN

Viena

Congreso; 13th Congress of ECCO; 2018

ECCO

BackgroundInflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn?s disease (CD)show an increased risk of thrombosis. PROS1 is a well-established anticoagulant. PlasmaPROS1 circulates in a free form that can function as an anticoagulant or in complex withthe complement C4b-binding protein (C4BP). Interestingly, PROS1 has also emerged asa potent anti-inflammatory mediator due to its function as agonist of the TAM receptortyrosine kinases (Rothlin 2015). Here, we aimed to test if IBD or subsets of IBD areassociated with reduced amounts of the anticoagulant and anti-inflammatory protein,PROS1. AIMS: to measure and compare free PROS1 and total C4BP levels in CD, UCand healthy controls and their relationship with activity status (Determined for indexes:CDAI, Mayo) and disease patterns (Montreal).MethodsFree PROS1 and C4BP (immunoturburbimetry, Liatest, Stago, France) were determinedin 103 IBD patients (45 M, 58 F, UC: n = 66, CD n = 37) and 30 healthy controls (18 M,12 F), mean ages: 37.5 ± 15.6, 41.4 ± 14.6, 38.2 ± 12.2, respectively.ResultsMean PROS1 levels in CD (89.9. ± 28.0) were significantly lower compared withcontrols (109.6 ± 23.9, p = 0.0019) and UC (104.4 ± 27.0, p = 0.0076). Within the CDgroup, a statistical difference vs. controls was observed in patients with active disease (n= 25, levels 84.9 ± 24.1, p = 0.0004), but not in patients in remission (n = 12: 100.2 ±33.5). Moreover, the moderate?severe subset (n = 21), presented the lowest levels (84.0 ±25.9) vs. controls p = 0.0006. In UC, PROS1 levels did not show differences betweensubsets (42 active, 24 remission: 101.1 ± 26.3 and 110.0 ± 27, respectively) or withcontrols. CD patterns (behaviour, location) and UC extent (12 proctitis, 54 moreextensive) did not show significant differences. C4BP levels were also found to bedecreased in CD (global sample, active patients, severe-moderate subsets: 98.6 ± 14.4,98.8 ± 12.0, 98.4 ± 12.6, 109.9 ± 8.8, p = 0.0004, p = 0.0008, p = 0.0014 vs. controls,respectively). Unlike PROS1, C4BP in UC (102.8 ± 9.9) was lower than in controls (p =0.0010) mainly in severe?moderate activity (p = 0.0322), and besides, no statisticaldifferences were observed between UC and CD.Conclusion(1) Free PROS1 levels were significantly lower in active CD vs. controls (especially inthe severe?moderate activity subsets), but in the case of UC the levels wereindistinguishable from controls. On contrary, C4BP levels were reduced in both diseases,particularly in patients with higher disease activity. (2) Decrease of Free PROS1 in CD,was not secondary to a potential C4BP-bound PROS1 for C4BP increase. (3) Futurestudies will aim to test if reduced levels of PROS1 in circulation might not onlycontribute to the increased risk of thrombosis but also to the enhanced inflammation inCD.