25rhk026 10.3205/25rhk026 urn:nbn:de:0183-25rhk0265 Meeting Abstract Kümmel Kümmel Marie Svenja MS

Justus Liebig University Gießen, Campus Kerckhoff, Department of Rheumatology and Clinical Immunology, Bad Nauheim

author Khodaverdi Khodaverdi Negar N

Justus Liebig University Gießen, Campus Kerckhoff, Department of Rheumatology and Clinical Immunology, Bad Nauheim

author Arnold Arnold Mona M

Justus Liebig University Gießen, Campus Kerckhoff, Department of Rheumatology and Clinical Immunology, Bad Nauheim

author Ohl Ohl Selina S

Justus Liebig University Gießen, Campus Kerckhoff, Department of Rheumatology and Clinical Immunology, Bad Nauheim

author Frommer Frommer Klaus K

Justus Liebig University Gießen, Campus Kerckhoff, Department of Rheumatology and Clinical Immunology, Bad Nauheim

author Schulz Schulz Nils N

Kerckhoff-Klinik, Rheumatologie, Bad Nauheim

author Rehart Rehart Stefan S

Agaplesion Markus Hospital, Dept. of Orthopaedics and Trauma Surgery, Frankfurt am Main

author Müller-Ladner Müller-Ladner Ulf U

Justus Liebig University Gießen, Campus Kerckhoff, Department of Rheumatology and Clinical Immunology, Bad Nauheim

author Neumann Neumann Elena E

Justus Liebig University Gießen, Campus Kerckhoff, Department of Rheumatology and Clinical Immunology, Bad Nauheim

author German Medical Science GMS Publishing House

Düsseldorf

610 20250917 engl This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). M0627 026 Deutsche Gesellschaft für Rheumatologie Deutsche Gesellschaft für Orthopädische Rheumatologie 53. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 39. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh) Deutscher Rheumatologiekongress 2025 Experimentelle & Translationale Rheumatologie Wiesbaden 20250917 20250920 ET.05 TextIntroduction: Rheumatoid arthritis (RA) synovial fibroblasts (RASF) contribute to inflammation and cartilage degradation in RA. Our research indicates that RASF from patients in remission exhibit reduced levels of interleukin-36β (IL-36β). IL-36β plays a crucial role in immune regulation and was evaluated regarding its effects on RASF.Methods: RA patients were classified as in remission or active RA according to clinical and laboratory parameters. RNA sequencing was performed on RASF from both patients groups with/without stimulation with 0.05ng/ml IL-1β followed by pathway analysis and top 50 dysregulated genes. Adhesion assays for 6h with 1ng/ml IL-1β and/or IL-36β pre-treated RASF were performed for 2 h and the number of adhesive RASF quantified. Pre-stimulated RASF were compared after migration through 8µm membranes towards an FBS gradient. The surface of crystal violet stained RASF was quantified. Proliferation was measured using RASF stimulated with IL-1β or/and IL-36β. After 19–24 h, the BrdU-assay was performed. To evaluate differences of the IL36 receptor (IL-36R) expression, immunofluorescence of synovial tissues from RA (active/remission) and osteoarthritis patients were performed and signal intensity and area of signal/visual field measured.Results: RNA sequencing revealed that RASF from patients in remission showed significantly lower levels of IL-36β and IL-36Ra compared to patients with active disease (n=4). RA-36R was increased in RA tissue from patients with active disease. IL36R was primarily located in the lining layer in all synovial tissues. Patients with active RA had stronger IL36R signals. IL-36β-stimulated RASF showed significantly lower adhesion compared to unstimulated cells and IL-1β-stimulated cells (p<0.0075, n=14). IL-36β-stimulated RASF showed significantly increased migration compared to unstimulated controls (p<0.002, n=14). IL-36β-stimulated RASF from patients in remission showed significantly increased migration compared to unstimulated controls (p<0.026, n=7). Proliferation was increased in IL36β-stimulated cells compared to controls with no difference between active disease and remission.Conclusion: The altered migration and adhesion of IL-36β-stimulated cells suggests a potential for increased migration towards sites of tissue destruction in RA. The increased proliferation of RASF by IL36β, and the impaired IL36R synovial signal in patients with active disease highlights the pathogenicity of elevated IL36β levels observed in active disease. 0 0 0 0