Ab0792 Molecular and Cellular Insights of B Cell Lymphoma in Patients With Sjögren’s Syndrome

Background: Sjögren's syndrome, an autoimmune disorder characterized by lymphocytic infiltration and chronic inflammation of exocrine glands 1, increases the risk of B-cell lymphomas in primary Sjogren's Syndrome (pSS) 2. The causes for this heightened incidence in a subset of patients remain undefined, suggesting abnormal immune cell activation may contribute. We analyzed a transcriptomic dataset from pSS patients. Objectives: To elucidate the molecular mechanisms associated with B-cell lymphoma and characteristic immune cell populations within peripheral blood samples from patients diagnosed with pSS. Methods: We downloaded the GSE84844 dataset from the GEO platform. Employing the Gene Set Enrichment Analysis (GSEA) platform, we identified enriched genes associated with B-cell lymphoma. Further, we constructed Protein-Protein Interaction (PPI) networks using Cytoscape and identified hub genes through the Cytohubba plugin. Transcription factors that modulate the network were found using the iRegulon plugin. To discern differences in immune cell populations between pSS and healthy controls (HC), we used CibersortX. For statistical analysis, we used SPSS 25th edition. Significant differences between groups were identified using parametric or nonparametric tests upon normality testing with Kolmogorov-Smirnov. All utilized software is free-access and available to the public. Results: 30 HCs and 30 pSS patients were included. The mean age for HC was 39.33±9.44, while for pSS, was 61.07±10.8. The mean ESSDAI score was 1.77±2.62, with 24 patients testing positive for RO/SSA and 13 testing positive for LA/SSB. 10 genes were enriched in this cohort of patients. Moreover, UBE2V1 and SRF were identified as transcription factors that target 7 out of the 10 genes, as seen in Figure 1. Regarding digital cytometry, significant differences were found in populations of memory B cells, CD8+ T cells, CD4+ Naive T cells, resting NK cells, CD4+ memory activated T cells, regulatory T cells, and gamma delta T cells (Table 1). Conclusion: In this investigation, a set of 10 genes linked to B-cell lymphoma enrichment was found. Digital cytometry identified differences between immune cell populations within the blood samples. Further investigation is needed to expand our understanding of the molecular mechanisms that contribute to B-cell lymphoma. REFERENCES: 1 Tasaki, Shinya, et al. "Multiomic Disease Signatures Converge to Cytotoxic CD8 T Cells in Primary Sjögren's Syndrome." Annals of the Rheumatic Diseases, U.S. National Library of Medicine, Aug. 2017, www.ncbi.nlm.nih.gov/pmc/articles/PMC5738597/#s4title. 2 Lee, Kristen. "Sjögren's Syndrome." American College of Rheumathology, Feb. 2023, rheumatology.org/patients/sjogrens-syndrome. Acknowledgements: NIL. Disclosure of Interests: None declared.