OP0271 Gastrointestinal damage and microbial translocation are involved in the development of immune system activation in inflammatory bowel disease-associated spondyloarthritis

Background The altered composition of the gastrointestinal (GI) microbiota, known as dysbiosis, can induce and modulate the systemic inflammation, through microbial translocation and T-cell activation, in several immuno-mediated diseases, such as inflammatory bowel disease (IBD), HIV infection, and ankylosing spondylitis. Objectives In a cohort of 85 patients with inflammatory bowel disease-associated spondyloarthritis (SpA/IBD), we assessed gut bacterial infiltration and intestinal damage. In systemic circulation, GI epithelial damage, microbial translocation and immune system activation were assessed with intestinal-fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), soluble CD14 (sCD14), respectively. Moreover, the in vitro activity of the latter two was evaluated on osteoblast cells. Methods I-FABP, LPS, sCD14, sclerostin (SOST) and anti-SOST antibodies (anti-SOST-IgG) were assayed with ELISAs. LPS and sCD14 were used in vitro to stimulate the MG63 human osteoblast-like cell line. Occludin, claudin-1, claudin-4, and the presence of bacteria were assessed, respectively, by real-time-PCR analysis and immunohystochemical staining of the ileum. Results Bacteria were detectable in the ileal epithelium of IBD patients, but only in SpA/IBD they were associated with epithelial damage and downregulation of occludin, claudin-1 and claudin-4 (figure 1A-B). The serum levels of I-FABP, LPS and sCD14 resulted significantly higher in axial (187.9, 14.03, and 26.97, respectively) and peripheral SpA/IBD (130.3, 11.55, and 18, respectively) than in IBD patients (IFABP 43.65, p In the SpA/IBD cohort, SOST was weakly correlated with I-FABP (r=-0.2683), LPS (r=-0.3063) and sCD14 (r=-0.3075), and anti-SOST-IgG with LPS (r=- 0.3959) and sCD14 (r=-0.3414). Moreover, sCD14 showed significant correlation with I-FABP (r=0.3316) and LPS (r=0.5649). In vitro , LPS, but not sCD14, significantly induced SOST expression through the upregulation of both Wnt3a and Wnt5a and the downregulation of the b-catenin proteins (figure 1D). On the opposite, the combination of LPS and sCD14 downregulated SOST expression through the upregulation of ERK1/2 and b-catenin protein (figure 1D). Conclusions The role of gut inflammation and microbial translocation in the onset of arthritis in IBD patients are still under investigation. We have demonstrated that in SpA/IBD there is a significant bacterial infiltration of the ileal tract, associated with the downregulation of tight-junctions’ proteins (occludin, claudin-1 and claudin-4) and epithelial damage, that cause microbial translocation and higher plasma levels of I-FABP, LPS, and sCD14. LPS and sCD14, thus, could trigger a complex systemic inflammatory response acting on several biochemical pathways, linking the immune system (anti-SOST-IgG) and the bone (SOST). Disclosure of Interest None declared