Abstract

Background: Recent evidence suggests the existence of increased intestinal permeability (IP) and bacterial translocation (BT) in patients with juvenile idiopathic arthritis (JIA). Similar observations have been reported in adult patients with rheumatoid arthritis (RA) and spondyloarthritis. In adults, serum zonulin, a physiological modulator of intestinal epithelial tight junctions, has been identified as an element involved in this hyperpermeability. This modification of the intestinal barrier is thought to lead to BT, for which certain markers, lipopolysaccharide (LPS) and soluble CD14 (sCD14), are increased in RA patients. Objectives: The aim of this study was to investigate IP, BT and intestinal barrier integrity in JIA patients in transition. Methods: Clinical data and sera from a single centre retrospective cohort of consecutive JIA patients transitioning to adult rheumatology were studied. IP, BT and intestinal integrity were assessed by measuring serum concentrations (ELISA) of zonulin, soluble CD14 and iFABP. These intestinal markers were also measured in the serum of healthy volunteers. Differences between the two groups and correlations were assessed using Student's t-test and Pearson's test or Mann-Whitney and Spearman's tests, depending on the distribution of the subgroups studied. Results: We identified 120 JIA patients (19±5 years) and 40 controls (48.7±9.2 years). The mean age at diagnosis of JIA was 9 (±6) years. There were 18 (15%) oligoarticular JIA, 17 (14%) extensive oligoarticular JIA, 17 (14%) enthesitis-related arthritis (ERA), 16 (13%) systemic JIA, 14 (12%) FR+ polyarticular JIA and 14 (12%) FR- polyarticular JIA. Concentrations of zonulin (6.5 vs 5.8 ng/ml, p=0.9), iFABP (1570 vs 1632 ng/ml, p=0.14) and soluble CD14 (2300 vs 2296 ng/ml, p=0.61) were not different between the JIA and control groups. The concentration of zonulin was higher in the systemic JIA group compared to all other forms of JIA (n=16, 6.6 [4-32] vs 1.8 [1-4.3] ng/ml, p=0.0058) and controls (6.6 [4-32] vs 5.8 (5-11) ng/ml, p=0.04). There was no difference in iFABP and soluble CD14 levels between oligo- and polyarticular or systemic JIA and controls. There was no correlation between zonulin concentration and CRP or IL-6 in either the all JIA group (r=-0.06, p=0.75) or the systemic JIA group (r=0.4, p=0.39). There was no difference in zonulin concentration between JIA patients with or without NSAIDs (3.3 [1-5.9] vs 1.7 [1.3-7.2] ng/ml, p=0.9) and those with or without corticosteroids (2.7 [0.4-9.8] vs 1.7 [1.3-7.2] ng/ml, p=0.74). Finally, zonulin levels did not differ between JIA patients on biotherapies and those on csDMARDs (2.1 [0.8-3.3] vs 1.4 [1.3-7.2] ng/ml, p=0.41), nor between those with disease duration of more vs less than 5 years (4 [1.5-9.1] vs 2 [1-4.4] ng/ml, p=0.06). Conclusion: Our findings are consistent with the literature suggesting an involvement of the intestinal barrier in chronic inflammatory rheumatism. This is the first study in adult JIA patients to demonstrate an increase in markers of intestinal hyperpermeability in systemic forms This increase in IP is not associated with an increase in BT, as recently shown in spondyloarthritis, and is not correlated with systemic inflammation. These data may pave the way for new therapies modulating intestinal barrier. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Sophie Hecquet BMS, UCB, Galapagos, Marion Thomas: None declared, Eleonore Parisel: None declared, Alice Combier: None declared, Julien Wipff: None declared, Anne Cauvet: None declared, Gertrude Touanga: None declared, Frank Verhoeven: None declared, Céline Demougeot: None declared, Pierre Quartier: None declared, Jerome Avouac: None declared, Yannick Allanore: None declared.