Sjögren's disease: an autoimmune disease

Academic presentation on Sjögren's disease: an autoimmune disease

1. THERAPEUTIC INTERVENTIONS TARGETING SJÖGREN'S SYNDROME Group 2

2. OUR TEAM Durba Saha Sumaiya Afrin Jiba Nowfat Tasfiah Tasfia Rehnuma Oritri Immune Pathophysiology Therapeutic Targets Mode of Action of Therapeutic Molecule Futuristic Therapeutic Possibilities

3. WHAT IS SJÖGREN'S SYNDROME?

4. Innate immune system : Interferons (IFNs) Toll-like receptors (TLRs) Adaptive immune system : T helper 17 (Th17) cells B cells PATHOPHYSIOLOGY

5. INFLAMMATORY PROCESS Cytokines (TNF-α, IL-6, and IL-17) Oxidative stress (ICAM-1 and PD-L112) Cellular infiltration (salivary and lacrimal glands)

6. OUTCOME Glandular Dysfunction -Reduced Saliva Production -Reduced Tear Production Systemic Effects

7. THE POSSIBLE THERAPEUTIC TARGETS (TARGETING THE IMMUNE SYSTEM) TARGETING THE INTERFERON PATHWAY TARGETING B CELLS TARGETING T CELL SIGNALLING

8. Mode of Action of Therapeutic M olecules Targeting the Interferon pathway: Therapeutic molecule: Anifrolumab Targets Type I Interferon Pathways Blocks Transcription of ISG ( Interferon Stimulated Genes ) Reduced JAK-STAT activation Decreased inflammation Treatment of glandular damage

9. Mode of Action of Therapeutic molecules Targeting B Cells: Therapeutic molecule: Rituximab Antibody Dependent Cellular Cytotoxicity - RTX-CD20 binding triggers NK cells Direct Cross Linking of CD20 by RTX on B cells - RTX-CD20 binding on multiple B cells Complement Dependent Cytotoxicity - RTX-CD20 activates complement system Phagocytosis by Macrophages

10. Future Therapeutic Possibilities Seletalisib: Target: Phosphatidylinositol 3-kinase delta pathway Reduce lymphocytes, plasma cells, autoantibodies, lymphoid chemokines and cytokines Parsaclisib: Target: Phosphatidylinositol 3-kinase delta pathway Reduce autoreactive B cells and autoantibodies Mesenchymal stem cell transfusion: Target: Th1, Th17 and T follicular helper cells Reduce inflammatory cytokines and decrease anti-inflammatory cytokines

11. References Baldini, C., Fulvio, G., Rocca, G. L., & Ferro, F. (2024). Update on the pathophysiology and treatment of primary Sjögren syndrome. Nature Reviews Rheumatology . https://doi.org/10.1038/s41584-024-01135-3 Gürcan, H. M., Keskin, D. B., Stern, J. N. H., Nitzberg, M. A., Shekhani, H., & Ahmed, A. R. (2009). A review of the current use of rituximab in autoimmune diseases. International Immunopharmacology, 9 (1), 10–25. https://doi.org/10.1016/j.intimp.2008.10.004 Siebeler, R., Menno, & Hoeksema, M. A. (2023). The regulatory landscape of macrophage interferon signaling in inflammation. Journal of Allergy and Clinical Immunology, 152 (02). https://doi.org/10.1016/j.jaci.2023.04.022 Zhan, Q., Zhang, J., Lin, Y., Chen, W., Fan, X., & Zhang, D. (2023). Pathogenesis and treatment of Sjogren's syndrome: Review and update. Frontiers in immunology , 14 . https://doi.org/10.3389/fimmu.2023.1127417 Zhao, T., Zhang, R., Li, Z., Qin, D., & Wang, X. (2024). Novel and potential future therapeutic options in Sjögren's syndrome. Heliyon, 10 (19). https://doi.org/10.1016/j.heliyon.2024.e38803

12. QUESTION T IME

13. THANK YOU