Ab0927 Serum Interleukin-40 Levels in Patients With Inflammatory Bowel Diseases-Associated Spondyloarthritis: A Preliminary Study

Background: Inflammatory bowel diseases (IBD)-associated with spondyloarthritis (SpA) are group of chronic immune-mediated inflammatory diseases that significantly impact patients' quality of life. Understanding the pro-inflammatory mechanisms underlying this association for gaining insight into its nature, facilitating early diagnosis, and recognizing SpA in IBD patients. Interleukin 40 (IL-40) is a novel cytokine associated with autoimmune rheumatic disorders, inflammation and tissue remodelling. Furthermore, studies in mice have identified a link between IL-40 expression and the gut microbiome [1]. Thus, we aimed to analyse the implication of IL-40 in SpA-IBD. Objectives: The aim of this preliminary study was to analyse IL-40 in the serum of patients with IBD and those with SpA-IBD, exploring its potential association with clinical parameteres. Methods: A cohort of 29 patients with SpA-IBD 20 patients with IBD and 52 healthy controls (HC) was selected for the purpose of this preliminary study. The levels of IL-40 were measured using a commercially available ELISA kit. Inclusion criteria for patients involved meeting the modified New York criteria or Assessment of SpondyloArthritis International Society (ASAS) classification for SpA and fulfilling clinical, radiological, histological and/or endoscopic criteria for IBD. Disease activity was determined using C-reactive protein (CRP) and serum calprotectin levels. For IBD patients, clinical activity was assessed using the Harvey Bradshaw Index/Total Mayo score, and endoscopic activity was measured using the Simple Endoscopic Score for Crohn's Diseases/Mayo score. Results: Serum IL-40 levels were significantly higher in patients with IBD compared to those with SpA-IBD and HC [3.89 (1.92-5.85) vs. 2.30 (1.14-3.29) and 1.85 (1.17-2.67) ng/ml; p<0.01 and p<0.0001, respectively]. Additionally, we found association between IL-40 levels and serum CRP (r=0.481, p=0.032), serum calprotectin (r=0.473, p=0.035), and intestinal score activity (r=0.508, p=0.022). Additionally, there was a trend for correlation between IL-40 levels and the Total Mayo score - DAI in patients with ulcerative colitis (r=0.521, p=0.070). While the elevation of IL-40 in the serum of SpA-IBD patients did not reach significance compared to HC; we observed a negative correlation of IL-40 with the components of spinal mobility such as Schober (r=-0.515, p=0.004), chest expansion (r=-0.466, p=0.011), and positive correlation with distance chin-sternum (r=0.407, p=0.029). Patients with enthesitis tended to have higher levels of IL-40 compared to those without enthesitis (p=0.08). Furthermore, SpA-IBD patients with higher levels of IL-40 (cut-off 2.5 ng/ml) exhibited increased parameters of systemic inflammation, including ESR (p=0.02) and CRP (p=0.09). Conclusion: The newly discovered cytokine IL-40 shows potential associations with pro-inflammatory activity in IBD and SpA. Further research is needed to elucidate the precise role of IL-40 in the immunopathogenesis of enteropathic SpA. REFERENCES: [1] Catalan-Dibene J, McIntyre LL, Zlotnik A. Interleukin 30 to Interleukin 40. J Interferon Cytokine Res. 2018 Oct;38(10):423-439. doi: 10.1089/jir.2018.0089. PMID: 30328794; PMCID: PMC6206549. Acknowledgements: This work was supported by Ministry of health Czech Republic [NU21-05-00276, 023728]; Ministry of Education, Youth and Sports Czech Republic [SVV-260638] and BBMRI.cz, reg.no. [LM2023033]. Disclosure of Interests: None declared.