Pos0134 Systemic Inflammatory Cytokine Profiles in Patients With Gout During Flare, Intercritical, and Treat-to-Target Phases: Tnfsf14 as New Biomarker

Background: Untreated gout is characterized by monosodium urate (MSU) crystal accumulation responsible for recurrent flares that are commonly separated by asymptomatic phases. Both phases are inflammatory conditions of variable intensity. Gout flares are self-limited inflammatory reactions involving multiple mediators. Objectives: This study aimed to characterize the inflammatory profiles of gout disease at 3 different phases. Methods: Using the Olink targeted proteomics, levels of 92 inflammation-related proteins were measured in plasma samples of a prospective gout population (GOUTROS), collected at the onset of gout flare (T1), the intercritical phase (T2), and after reaching the serum urate target level under urate-lowering therapy (T3). Results were validated in an independent cohort. Ex vivo and in vitro experiments were performed to assess the inflammatory properties of new biomarkers. Results: In total, 21 inflammatory new biomarkers were differentially expressed during the 3 gout phases. The levels of 4 of these proteins (interleukin 6 [IL-6], colony-stimulating factor 1, vascular endothelial growth factor A and tumour necrosis factor superfamily 14 [TNFSF14]) were increased during gout flare in an independent cohort. IL-6 and TNFSF14 had the highest fold change in expression during T1 versus T2 or T3. TNFSF14 concentration was higher in synovial fluids collected during gout flare than during osteoarthritis (283.7 ±559.1 vs 10.8 ±31.1 pg/ml, p<0.001). Similarly, TNFSF14 expression was higher in mouse air pouch membranes collected after MSU crystal stimulation than after saline stimulation. These results suggested that TNFSF14 was produced locally at the inflamed joint. In vitro, recombinant TNFSF14 protein enhanced the inflammatory response of human PBMCs exposed to lipopolysaccharide and MSU crystal stimulation. Conversely, TNFSF14 blockade reduced the inflammatory response. Additionally, single nucleotide polymorphisms of TNFSF14 affected the ability of myeloid cells to produce inflammatory cytokines. PBMCs collected from individuals carrying rs344559 exhibited decreased production of IL-1β, while PBMCs collected from individuals carrying rs2101765 showed increased production of IL-1β and IL-6. Conclusion: This study helps to improve the understanding of how the human immune system reacts in different stages of gout, allowing the identification of TNFSF14 as a new biomarker associated with gout flare. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.