26rhk04910.3205/26rhk049urn:nbn:de:0183-26rhk0499Meeting AbstractMulti-omics profiling and machine learning identify dual homeostatic defects in recurrence of giant cell arteritisGheitasiGheitasiRezaRUniversität Bonn, Uniklinikum Bonn, Medizinische Klinik und Poliklinik III Innere Medizin mit den Schwerpunkten Onkologie, Hämatologie und Rheumatologie, Bonn, DeutschlandauthorBauerBauerClaus-JürgenCJUniversität Bonn, Uniklinikum Bonn, Medizinische Klinik und Poliklinik III Innere Medizin mit den Schwerpunkten Onkologie, Hämatologie und Rheumatologie, Bonn, DeutschlandauthorPetzinnaPetzinnaSimon M.SMUniversität Bonn, Uniklinikum Bonn, Medizinische Klinik und Poliklinik III Innere Medizin mit den Schwerpunkten Onkologie, Hämatologie und Rheumatologie, Bonn, DeutschlandauthorKirchKirchSophie-MarieSMUniversität Bonn, Uniklinikum Bonn, Medizinische Klinik und Poliklinik III Innere Medizin mit den Schwerpunkten Onkologie, Hämatologie und Rheumatologie, Bonn, DeutschlandauthorZahmatkeshZahmatkeshMozhganMUniversität Bonn, Uniklinikum Bonn, Medizinische Klinik und Poliklinik III Innere Medizin mit den Schwerpunkten Onkologie, Hämatologie und Rheumatologie, Bonn, DeutschlandauthorHerwig-CarlHerwig-CarlMartinaMUniversity of Bonn, University Hospital Bonn, Department of Ophthalmology, Division of Ophthalmic Pathology, Bonn, DeutschlandauthorSchäferSchäferValentin SebastianVSUniversität Bonn, Uniklinikum Bonn, Medizinische Klinik und Poliklinik III Innere Medizin mit den Schwerpunkten Onkologie, Hämatologie und Rheumatologie, Bonn, DeutschlandauthorGerman Medical Science GMS Publishing House
Düsseldorf
61020260909englThis 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).M0656049Deutsche Gesellschaft für RheumatologieDeutsche Gesellschaft für Orthopädische RheumatologieGesellschaft für Kinder- und Jugendrheumatologie54. Kongress der Deutschen Gesellschaft für Rheumatologie und Klinische Immunologie (DGRh), 36. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR), 40. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh)Deutscher Rheumatologiekongress 2026Experimentelle & Translationale RheumatologieLeipzig2026090920260912ET.25TextIntroduction: The relapse rate of giant cell arteritis (GCA) remains a major clinical challenge , largely due to an incomplete understanding of the mechanisms driving the failure of immune homeostasis. While the acute inflammatory response is well-characterized , the precise molecular defects preventing the termination of pathogenic signaling are undefined.Methods: To delineate the hierarchical molecular layers of homeostatic failure, high-resolution proteomics and bulk RNA sequencing were performed on peripheral blood mononuclear cells (PBMCs) and serum from participants, including treatment-naïve, drug-free remission, and relapsing GCA patients, alongside matched healthy controls. Functional ex vivo assays and supervised machine learning algorithms were utilized to validate pathway dysregulation.Results: Active GCA is characterized by systemic saturation of serum amyloid A (SAA) (Figure 1a ) and transcriptional dysregulation of the formyl peptide receptor 2 (FPR2) (Figure 1b ). RNA sequencing revealed that this transcript dysregulation is driven by a disease specific FPR2 bias, resulting in a loss of surface receptor responsiveness. Upon SAA re-exposure in remission PBMCs displayed an explosive 32-fold upregulation of interleukin (IL)-23 compared to active disease (Figure 1c ). Furthermore, while clinical remission restores FPR2 receptor functionality, it fails to correct a persistent defect in the suppressor of cytokine signaling 3 (SOCS3) intracellular checkpoint (Figure 1d ). Treatment with the FPR2 agonist successfully suppressed pathogenic IL-23 secretion in remission but failed in the refractory active disease state (Figure 1e ). Lastly, machine learning approach confirmed that clinical recurrence is a highly accurate molecular recapitulation of the primary disease state, driven by the re-engagement of SAA in a homeostatically incompetent environment.Conclusion: During active GCA pathogenic IL-23 upregulation is driven by dual homeostatic defects and intracellular SOCS3 signaling failure. These findings establish that durable clinical remission requires the active restoration of homeostatic signaling competence rather than broad immunosuppression alone.Bilton EJMollan SPGiant cell arteritis: reviewing the advancing diagnostics and management2023Eye (Lond)2365-2373Bilton EJ, Mollan SP. Giant cell arteritis: reviewing the advancing diagnostics and management. Eye (Lond). 2023 Aug;37(12):2365-2373. DOI: 10.1038/s41433-023-02433-yhttp://dx.doi.org/10.1038/s41433-023-02433-yMastromarino MLacivita EColabufo NALeopoldo MG-Protein Coupled Receptors Involved in the Resolution of Inflammation: Ligands and Therapeutic Perspectives2020Mini Rev Med Chem2090-2103Mastromarino M, Lacivita E, Colabufo NA, Leopoldo M. G-Protein Coupled Receptors Involved in the Resolution of Inflammation: Ligands and Therapeutic Perspectives. Mini Rev Med Chem. 2020;20(20):2090-2103. DOI: 10.2174/1389557520666200719014433http://dx.doi.org/10.2174/1389557520666200719014433011
Figure 1: The serum amyloid A-formyl peptide receptor 2 axis in giant cell arteritis. (a) Differential expression of serum amyloid A isoforms in patient serum across disease phases. (b) Transcriptional upregulation of the resolution receptor formyl peptide receptor 2 in active disease. (c) Paradoxical interleukin-23 fold change induction following serum amyloid A stimulation in different disease stages. (d) Defective induction of the suppressor of cytokine signaling 3 in remission cohort. (e) The formyl peptide receptor 2 agonist effect on interleukin-23 protein secretion in remission state.