25rhk039 10.3205/25rhk039 urn:nbn:de:0183-25rhk0391 Meeting Abstract Song Song Ruoyu R

Heidelberg University Hospital, Medical Clinical 5, Heidelberg

author Yang Yang Zhihua Z

Heidelberg University Hospital, Medical Clinical 5, Heidelberg

author Lu Lu Junyan J

Medizinischen Fakultät Heidelberg, Institute for Computational Biomedicine, Heidelberg

author Lorenz Lorenz Hanns-Martin HM

Heidelberg University Hospital, Medical Clinical 5, Heidelberg

author Carvalho Carvalho Rui R

Heidelberg University Hospital, Medical Clinical 5, Heidelberg

author Souto-Carneiro Souto-Carneiro Margarida M

Heidelberg University Hospital, Medical Clinical 5, Heidelberg

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 039 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.19 TextIntroduction: Rheumatoid arthritis (RA) is a complex autoimmune disease with significant immune and metabolic dysregulation , . While most research has focused on female patients, male RA patients exhibit unique immune characteristics that remain poorly understood. This study aims to investigate the immune and metabolic features of male RA patients by analyzing mitochondrial protein expression in T and B cells and performing transcriptomic analysis to compare RA male patients with healthy male controls.Methods: We utilized existing total RNA transcriptome data from the GEO database (GSE89408), performed on joint synovial biopsies from subjects with and without RA. The study involved the identification of differentially expressed genes (DEGs) using bioinformatics tools, followed by KEGG and GO enrichment analysis. Ex vivo protein expression levels of TOMM20 and MT-ND1 in T cells and B cells from male patients were determined by Western blot (WB) analysis.Results: WB analysis showed no significant difference in TOMM20 expression between T and B cells. MT-ND1 expression was slightly higher in B cells compared to T cells, but the difference was not statistically significant, suggesting that both T and B cells might have similar mitochondrial metabolism in RA, as shown in Figure 1 . Bioinformatics analysis identified differentially expressed genes (DEGs) in male RA patients, with GO enrichment analysis highlighting pathways such as cytokine activity, immune receptor activity, chemokine binding, antigen binding, and complement activation. KEGG analysis revealed significant involvement in immune-related pathways, including B cell receptor signaling and phagocytosis, indicating altered immune regulation in the synovial membrane of male RA patients, as shown in Figure 2 .Conclusion: These findings suggest that regardless of their distinct immune functions both T and B cells in male RA patients have comparable mitochondrial metabolism. Whether this differs from healthy male individuals and female RA patients must be further explored. Nonetheless, the transcriptomic analysis of the synovial membrane clearly shows an immune dysregulation in RA, particularly in cytokine signaling and B cell activation. This study provides new insights into the immune-metabolic landscape of male RA patients and highlights potential pathways for further investigation in RA pathogenesis and targeted therapy. Weyand CM Goronzy JJ Immunometabolism in early and late stages of rheumatoid arthritis 2017 Nat Rev Rheumatol 291-301 Weyand CM, Goronzy JJ. Immunometabolism in early and late stages of rheumatoid arthritis. Nat Rev Rheumatol. 2017 May;13(5):291-301. DOI: 10.1038/nrrheum.2017.49 http://dx.doi.org/10.1038/nrrheum.2017.49 Gravallese EM Firestein GS Koscal N Ling E Longo DL Messenger LA Schubach A What Is Rheumatoid Arthritis? N Engl J Med 2024 Gravallese EM, Firestein GS, Koscal N, Ling E, Longo DL, Messenger LA, Schubach A. What Is Rheumatoid Arthritis? N Engl J Med. 2024 Apr 4;390(13):e32. DOI: 10.1056/NEJMp2310178 http://dx.doi.org/10.1056/NEJMp2310178 0

1 1 Figure 1: Western blot analysis of mitochondrial proteins in T and B cells from male RA patients and healthy male controls. (A) WB bands showing the expression of TOMM20 and MT-ND1 in isolated T and B cells. HSP90 was served as a loading control. (B) Quantification of protein expression levels relative to HSP90. No significant difference was observed in TOMM20 expression between T and B cells. Data are presented as mean ± standard deviation (SD). Analysis was performed using Student t-test (p < 0.05 was considered significant).

2 2 Figure 2: GO enrichment analysis of differentially expressed genes in the synovial membrane of male RA Patients when compared with healthy (non-arthritis) donors.

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