POS0069 INCREASED T CELL RESPONSES, METABOLIC ACTIVITY AND FIBROBLAST INVASIVE CAPACITY IN CHILDREN WITH DOWN’S SYNDROME-ASSOCIATED ARTHRITIS COMPARED TO JUVENILE IDIOPATHIC ARTHRITIS

Background: Juvenile idiopathic arthritis (JIA) was thought to be the most common inflammatory in children (Shih et al. , 2019). However an aggressive, erosive of little-known immunologic mechanism occurs 20 times more frequently with Down’s syndrome (Foley Objectives: This study undertaken characterize immune cell responses and synovial fibroblast invasiveness syndrome-associated (DA). Methods: Multiparametric flow cytometric analysis used examine peripheral blood T cell, B monocyte populations. In addition, cytokine their metabolic profile DA, JIA, Syndrome (trisomy 21 [T21]), healthy controls were assessed. The function DA primary fibroblasts (FLS) assessed response stimulation pro-inflammatory mediators alone combination (TNF-α, IL-17a, IFN-γ, GM-CSF). two major energy pathways glycolysis (ECAR) oxidative phosphorylation (OCR) quantified by Seahorse XFe96 Analyser. Migration, adhesion, invasion cytokine/chemokine secretion wound repair scratch assays, Transwell collagen chambers, adhesion binding ELISAs. Results: frequencies higher compared JIA T21 contrast which decreased. characterized increased CD4 + CD8 TNF- α, IFN- γ GM-CSF producing cells. frequency helper (Tph) cells elevated all other groups. parallel, increase evident mTOR pathway components AKT, S6. Comparison FLS demonstrated that display a invasive/migratory capacity are metabolically active. Based on cells, we next examined effect derived cytokines TNF-α, IL-17A, IFN-γ function. IL-17a induced IL-6, RANTES MCP-1 secretion, no observed for GM-CSF. Furthermore, TNF-α IL-17A migration PBMC FLS. Finally IL17A potentiated IL-6 stimulations alone. Conclusion: is aggressive form JIA. It invasive phenotype further inducing pathogenic mechanisms. These effects mirror disease clinically. References: [1]Foley, C. (2019) ‘Increased plasticity dysregulation follicular helper, regulatory Down arthritis’, Arthritis & Rheumatology pp. 0–1. doi: 10.1002/art.41150. [2]Shih, Y. J. ‘Enthesitis-related category juvenile Taiwan presents persistent active disease’, Pediatric . Rheumatology. 10.1186/s12969-019-0363-0. Disclosure Interests: None declared.