POS0410 BIOMARKERS REFLECTING DISTURBED GUT BARRIER DIFFER IN PATIENTS WITH SPONDYLOARTHRITIS, CROHN’S DISEASE AND ACUTE ANTERIOR UVEITIS
Authors: J. Rademacher, C. Hempel, V. Rios Rodriguez, F. Proft, M. Protopopov, M. Torgutalp, H. Haibel, U. Pleyer, B. Siegmund, D. Poddubnyy
Journal: Annals of the Rheumatic Diseases (2021)

Background: Spondyloarthritides (SpA) are characterized by frequent extra-musculoskeletal manifestations (EMM) among them acute anterior uveitis (AAU) and Crohn’s disease (CD). Vice versa, about 50% of AAU and 20% of CD patients have concomitant SpA. SpA patients show gut dysbiosis together with frequent subclinical gut inflammation. Biomarkers reflecting disturbed gut barrier (intestinal-fatty acid binding protein (iFABP), lipopolysaccharide binding protein (LBP) and zonulin) were previously found to be elevated in patients with radiographic axial SpA (r-axSpA) (1). Objectives: To evaluate whether biomarkers reflecting leaky gut are altered in patients with AAU, CD and SpA compared to healthy controls and whether they differ between patients with EMM with and without concomitant SpA. Methods: A total of 100 patients from the German Spondyloarthritis Inception Cohort (GESPIC) were included – among them 20 patients with r-axSpA without EMM, 40 patients with CD and 40 patients with non-infectious AAU – out of which 19 and 20 patients, respectively, had concomitant SpA (11/8 and 20/0 axial/peripheral SpA, respectively). The GESPIC patients were compared to 20 age- and sex-matched healthy donors (HD). The following five serum biomarkers were analyzed with ELISA: calprotectin, iFABP, LBP, soluble CD14 (sCD14) and zonulin. Results: Patient characteristics are shown in Table 1. Serum levels of calprotectin, LBP, sCD14 and zonulin differed significantly between patients with r-axSpA, AAU and CD with and without concomitant SpA and HD (Figure 1). When comparing patients with EMM with and without underlying SpA, calprotectin serum levels were significantly elevated in CD patients with SpA (8.6µg/ml (SD 5.5µg/ml)) compared to CD patients without SpA (5.7µg/ml (SD 4.1µg/ml); Mann-Whitney U Test, p=0.031). Serum levels of the analyzed biomarkers did not differ between AAU patients with and without axSpA. Spearman rank correlation revealed a significant association between CRP and calprotectin (correlation coefficient r=0.230; p=0.012), LBP (r=0.596; p&lt;0.0001), sCD14 (r=0.428; p&lt;0.0001) and zonulin (r=0.221; p=0.016), respectively. Furthermore, LBP and zonulin serum levels correlated positively (r=0.208; p=0.023); as well as LBP and sCD14 levels (r=0.418; p&lt;0.0001). Table 1. Patient characteristics. Mean values (standard deviation) or absolute numbers are shown. CD + SpA CD r-axSpA AAU + axSpA AAU HD N 19 21 20 20 20 20 Age 39.1 (11.3) 38.7 (14.4) 38.4 (10.3) 39.6 (12.0) 39.2 (12.5) 38.6 (12.9) Male (%) 9 (47%) 9 (43%) 9 (45%) 9 (45%) 9 (45%) 9 (45%) HLA-B27 positive (%) 5 (26%) 3 (14%) 17 (85%) 17 (85%) 13 (65%) 2 (10%) CRP in mg/l 14.3 (25.6) 18.0 (41.8) 9.1 (11.3) 6.7 (9.9) 2.3 (3.4) 0.6 (0.7) ASDAS 2.8 (1.1) 3.2 (0.6) 2.2 (1.0) BASDAI 4.1 (2.2) 5.4 (1.2) 3.2 (2.4) Figure 1. Biomarkers reflecting disturbed gut barrier show distinct signatures in patients with acute anterior uveitis, Crohn’s disease and axial Spondyloarthritis. Kruskal Wallis Test; p values shown. Dunn-Bonferroni Post-Hoc analyses, significant pairwise differences are marked; * p&lt;0.05; **p&lt;0.01; ***p&lt;0.0001Conclusion: We found substantial differences in biomarkers reflecting disturbed gut barrier between with SpA, CD, AAU and healthy controls. The presence of SpA was associated with higher calprotectin serum levels in CD as compared to CD without SpA. References: [1]Ciccia F, et al. Dysbiosis and zonulin upregulation alter gut epithelial and vascular barriers in patients with ankylosing spondylitis. 2017. Acknowledgements: Dr. Judith Rademacher is participant in the BIH-Charité Clinician Scientist Program funded by the Charité –Universitätsmedizin Berlin and the Berlin Institute of Health. Disclosure of Interests: None declared