25rhk035 10.3205/25rhk035 urn:nbn:de:0183-25rhk0359 Meeting Abstract Nguyen Nguyen Phuong P

Klinik und Poliklinik für Endokrinologie, Nephrologie und Rheumatologie, Rheumatologie, Leipzig

author Apel Apel Hannah H

Klinik und Poliklinik für Endokrinologie, Nephrologie und Rheumatologie, Rheumatologie, Leipzig

author Braune Braune Laurin L

Klinik und Poliklinik für Endokrinologie, Nephrologie und Rheumatologie, Rheumatologie, Leipzig

author Hagemann Hagemann Tobias T

Helmholtz Institut für Adipositas, Metabolismus und Gefäßforschung, Leipzig

author Rothe Rothe Kathrin K

Klinik und Poliklinik für Endokrinologie, Nephrologie und Rheumatologie, Rheumatologie, Leipzig

author Wagner Wagner Ulf U

Klinik und Poliklinik für Endokrinologie, Nephrologie und Rheumatologie, Rheumatologie, Leipzig

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 035 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.14 TextIntroduction: The T cell repertoire of patients with rheumatoid arthritis (RA) is characterized by the expansion of large clones, possibly developed due to chronic (auto-)antigen stimulation . A comprehensive study of clonally expanded T cells could shed light on mechanisms of T-cell-mediated autoimmunity in RA.Methods: Single-cell sequencing of RNA, T cell receptor (TCR) and hashtags for CD4 and CD8 surface expression was performed in circulating T cells (RA n=3; healthy donors, HD n=2). Circulating T cells were isolated from blood samples for flow cytometry analysis (RA n=14, HD n=12). For 4 additional RA patients, blood and synovial fluid samples were available.Results: Clonality analysis revealed that in contrast to healthy individuals, RA patients have large T cell clones (³10 T cells with the same paired TCR sequence) more frequently in the CD4 than in the CD8 compartment (CD4 in 92.3% vs. 23.5% of all large T cell clones in RA vs. HD; p < 0.001). Interestingly, lack of CCR7 and CD27 expression is found in 94% and 85% of large clones in RA and HD, respectively, making this combination a useful global marker for large clonal expansion. We identified 1,651 genes differentially expressed in RA vs. HD clonally expanded CD4 T cells. Gene ontology analysis revealed type I interferon pathway (JAK1, IFITM2, STAT4) and granzyme-mediated signaling (GZMB, PRF1, FGFBP2) to be upregulated, whereas HLA-class-II expression (HLA-DRB1, HLA-DRB5, HLA-DRA) was downregulated in RA vs. HD expanded CD4 T cells (Figure 1 ).Flow cytometry analysis showed that CCR7-CD27- T cells accumulate in the joints of RA patients compared to the peripheral blood (29.5% vs. 5.5% of total T cells; p = 0.03). Validation of selected markers using flow cytometry confirmed Perforin to be significantly upregulated in RA compared to HD CCR7-CD27- T cells (37.9% vs 5.2% Perforin+ T cells; p = 0.001).Conclusion: Expansion of large T cell clones in RA predominantly occurs in the CD4 T cell compartment. Clonally expanded CD4 T cells in RA accumulate in the joint, upregulate interferon-related genes and are thus likely to contribute to inflammation. Wagner UG Koetz K Weyand CM Goronzy JJ Perturbation of the T cell repertoire in rheumatoid arthritis 1998 Proc Natl Acad Sci U S A 14447-52 Wagner UG, Koetz K, Weyand CM, Goronzy JJ. Perturbation of the T cell repertoire in rheumatoid arthritis. Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14447-52. DOI: 10.1073/pnas.95.24.14447 http://dx.doi.org/10.1073/pnas.95.24.14447 0

1 1 Figure 1: Differentially expressed genes in clonally expanded CD4 T cells of RA patients vs. healthy controls.

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