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Immune Modulatory Effects of PD-1/PD-L1 in Myasthenia Gravis: Insights From Peripheral Blood Mononuclear Cell
Jianing Li1, Xinyue Liu1, Feiteng Qi2
1Health Science Center, Ningbo University, Ningbo, China.
Abstract:
Myasthenia gravis (MG) is an autoimmune disease characterized by the production of antibodies targeting acetylcholine receptor (AChR)-associated proteins. The disorder involves various immune cells, including T cells, B cells, and dendritic cells (DCs). Programmed cell death protein 1 (PD-1) is one of the immune checkpoints and plays a crucial role in regulating immune cell activation and cell death. PD-L1, the ligand of PD-1, is critical for immune suppression through the transmission of inhibitory signals. These molecules are implicated in the pathogenesis of MG, prompting further investigation into the expression and functional roles of PD-1/PD-L1 in this disease. To investigate the role of PD-1/PD-L1 in MG pathogenesis, we collected peripheral blood mononuclear cells (PBMCs) from MG patients and analyzed PD-1/PD-L1 expression in various immune cells using flow cytometry (FACs). Our findings revealed that PD-1/PD-L1 expression was elevated in PBMCs from MG patients compared to healthy controls. We conducted a correlation analysis to examine the relationship between PD-1/PD-L1 expression and MG, based on measurements of anti-AChR-IgG levels, MG-specific cytokines, and routine blood tests. Our results showed that PD-1 expression in CD8+ T cells and PD-L1 expression in DCs were positively correlated with anti-AChR-IgG levels in MG serum. Additionally, PD-1/PD-L1 expression was correlated with parts of associated cytokines. Furthermore, PD-1 expression in B cells was positively correlated with lymphocyte counts in the peripheral blood. Moreover, exogenous recombinant human PD-L1 protein (rhPDL1) was found to suppress the expression of IL-1β and IL-4. Our findings underscore the potential therapeutic role of PD-1/PD-L1 agonists in the treatment of MG.
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