OBJECTIVE: To explore new markers of SLE activity and potential targets for SLE immunotherapy.
METHODS: Collect peripheral blood mononuclear cells (PBMCs) from SLE patients and healthy controls (HC). Use flow cytometry to detect CD39 and CD73 expression on B cell subsets and enzyme-linked immunosorbent assay (ELISA) to measure adenosine (ADO) concentrations in SLE patients\' serum. Compare CD39+CD73+ B cell subsets frequency and ADO concentrations in SLE patients and HC group. Additionally, analyze the correlation between CD39+CD73+ B cell subsets frequency and clinical laboratory parameters.
RESULTS: CD39 and CD73 are simultaneously highly expressed on CD19+ B cell subsets, with significantly lower frequency of CD39+CD73+ B cell subsets in SLE patients compared to HC group. This frequency negatively correlates with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), C-reactive protein (CRP), and anti-double-stranded DNA (anti-dsDNA) antibodies, while positively correlating with IgM and prothrombin time (PT). Additionally, the frequency of CD39+CD73+ B cell subsets is significantly negatively correlated with IL-6 and IFN-α. In vitro cell experiments demonstrate that adenosine significantly inhibits R848-induced inflammatory cytokine production in a dose-dependent manner.
CONCLUSIONS: The frequency of CD39+CD73+ B cell subsets of SLE patients is decreased, correlating with clinical laboratory parameters and disease activity. Simultaneously, ADO concentration in the patients\' serum is reduced. The CD39+CD73+ B cell/ADO pathway may represent a novel immunotherapy strategy for SLE.
目的:探索新的SLE活性标志物和SLE免疫治疗的潜在靶点。
方法:从SLE患者和健康对照(HC)收集外周血单核细胞(PBMC)。使用流式细胞术检测B细胞亚群上CD39和CD73的表达,并使用酶联免疫吸附试验(ELISA)测量SLE患者血清中腺苷(ADO)的浓度。比较SLE患者和HC组CD39+CD73+B细胞亚群频率和ADO浓度。此外,分析CD39+CD73+B细胞亚群频率与临床实验室指标的相关性。
结果:CD39和CD73在CD19+B细胞亚群上同时高表达,与HC组相比,SLE患者中CD39+CD73+B细胞亚群的频率显着降低。该频率与系统性红斑狼疮疾病活动指数(SLEDAI)呈负相关,C反应蛋白(CRP),和抗双链DNA(抗dsDNA)抗体,同时与IgM和凝血酶原时间(PT)呈正相关。此外,CD39+CD73+B细胞亚群频率与IL-6和IFN-α呈显著负相关。体外细胞实验证明腺苷以剂量依赖性方式显著抑制R848诱导的炎性细胞因子产生。
结论:SLE患者CD39+CD73+B细胞亚群频率降低,与临床实验室参数和疾病活动相关。同时,患者血清中的ADO浓度降低。CD39+CD73+B细胞/ADO途径可能代表了SLE的一种新型免疫治疗策略。