Li Jianing, Liu Xinyue, Qi Feiteng, Ren Yan, Zhang Yuanting, Shen Yaoyang, Liu Hua, Wang Yixuan, Zheng Rou, Ou Yangxiang, Wang Geng, Li Na
Health Science Center, Ningbo University, Ningbo, China.
Department of Neurology, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo, China.
FASEB J. 2025 Aug 15;39(15):e70827. doi: 10.1096/fj.202500887R.
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.
重症肌无力(MG)是一种自身免疫性疾病,其特征是产生针对乙酰胆碱受体(AChR)相关蛋白的抗体。该疾病涉及多种免疫细胞,包括T细胞、B细胞和树突状细胞(DCs)。程序性细胞死亡蛋白1(PD-1)是免疫检查点之一,在调节免疫细胞活化和细胞死亡中起关键作用。PD-1的配体PD-L1通过传递抑制信号对免疫抑制至关重要。这些分子与MG的发病机制有关,促使人们进一步研究PD-1/PD-L1在该疾病中的表达和功能作用。为了研究PD-1/PD-L1在MG发病机制中的作用,我们收集了MG患者的外周血单个核细胞(PBMCs),并使用流式细胞术(FACs)分析了各种免疫细胞中PD-1/PD-L1的表达。我们的研究结果显示,与健康对照相比,MG患者PBMCs中PD-1/PD-L1的表达升高。我们基于抗AChR-IgG水平、MG特异性细胞因子和常规血液检测结果进行了相关性分析,以研究PD-1/PD-L1表达与MG之间的关系。我们的结果表明,MG血清中CD8 T细胞中的PD-1表达和DCs中的PD-L1表达与抗AChR-IgG水平呈正相关。此外,PD-1/PD-L1表达与部分相关细胞因子有关。此外,B细胞中的PD-1表达与外周血淋巴细胞计数呈正相关。此外,发现外源性重组人PD-L1蛋白(rhPDL1)可抑制IL-1β和IL-4的表达。我们的研究结果强调了PD-1/PD-L1激动剂在MG治疗中的潜在治疗作用。