Background: Still’s disease is a systemic inflammatory disorder of unknown aetiology affecting both children and adults. Both innate and adaptative arms of the immune system are involved in the pathogenic mechanisms underlying this disease [1]. To date, little is known about the potential pathogenic role of interleukin (IL)-15 in the context of Still’s disease.

Objectives: In this study, we evaluated sera levels of IL-15 in patients with Still’s disease. We also assessed the IL-15 pathway in peripheral blood mononuclear cells (PBMCs) as well as of synovial tissues in patients with Still’s disease.

Methods: We assessed sera from patients with Still’s disease followed at the Rheumatology Division of L’Aquila (IT), and at the Immunology and Clinical Medicine Unit of Campus Biomedico of Rome (IT). We evaluated sera levels of IL-15 in patients with active disease (n=40), inactive disease (n=16), and healthy controls (HCs) (n=24) by ELISA. In addition, by a bulky RNA sequencing, key molecules of the IL-15 pathway (IL-15, IL-15RA, IL-2RB, JAK1, JAK3, STAT3, STAT5A, mTOR, PI3K, AKT1, KRAS, RAF, MAPK1, mTORC1, BCL-2, IFN-γ, TNF, c-myc, c-fos, NF-kB e IFN-γ) were assessed in PBMCs of patients with Still’s disease (n=4) and matched HCs (n=3). Finally, a bulky RNA sequencing was performed in synovial tissues from patients with Still’s disease (n=2) and matched HCs (n=2).

Results: Eighty serum samples from Still’s disease were analyzed. Sera levels of IL-15 were significantly higher in patients with active Still’s disease [median 9.35 pg/ml (4.32-19.76)] when compared with patients with inactive disease [4.23 pg/ml (2.27-12.34)] and HCs [7.194 pg/ml (4.21-10.11)] (p<0.005). In addition, the values of IL-15 correlated with the presence of macrophage activation syndrome (MAS) (r=0.347, p=0.001). Assessing mRNA relative expression in PBMCs, STAT5A, PI3K, RAS, RAF, NF-kB, appeared to be down-regulated in Still’s disease than HCs. By RNA-sequencing analysis in synovial tissues, we observed that IL-15, IL15RA, IL2RB, STAT5A, STAT3, TNF, IFN-γ, PI3K, RAS, RAF, and JAK3 were up-regulated in patients with Still’s disease than HCs.

Conclusion: Our results suggest that IL-15 could play a key role in the pathogenesis of Still’s disease, especially in active disease with MAS. The assessment of synovial tissues provided new insights into the possible role of IL-15 pathway as additional mechanistic disease step in these patients.

REFERENCES: [1] Ruscitti P, et al. Nat Rev Rheumatol. 2024; 20(2):116-132.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.