系统性红斑狼疮患者外周血CD19^(+)CD25^(+)Breg比例和细胞表面PD-1和PD-L1的表达及其与临床指标的相关性

The proportion of CD19^(+)CD25^(+)Bregs in peripheral blood and the expression of PD-1 and PD-L1 on cell surface in patients with systemic lupus erythematosus and their correlation with clinical indicators

目的 研究程序性死亡蛋白1(PD-1)与其配体PD-L1在系统性红斑狼疮(SLE)患者外周血CD19^(+)CD25^(+)调节性B细胞(Breg)的表达及临床意义。方法收集50例SLE患者和41例健康人(HC)外周血标本,采用流式细胞仪检测外周血中CD19^(+)CD25^(+)Breg的比例,以及CD19^(+)CD25^(+)Breg的PD-1、PD-L1表达,同时采集患者的临床表现和实验室指标等临床信息。使用免疫磁珠分选CD4^(+)T细胞与CD19^(+)B细胞,体外细胞共培养,检测Breg的分化。结果SLE患者活动组外周血中CD19^(+)CD25^(+)Breg比例低于HC,CD25^(+)B细胞PD-1、PD-L1的表达高于HC;SLE患者有胸腔积液、关节炎、C反应蛋白(CRP)上升的患者Breg频率高于对应阴性组;SLE患者有IgM下降、抗核糖核蛋白(RNP)抗体阳性的患者Breg频率低于对应阴性组;SLE患者有感染、发热、关节炎、IgA上升的患者CD19^(+)CD25^(+)PD-1^(+)细胞频率高于对应阴性组;SLE患者有感染、发热、IgA上升的患者CD19^(+)CD25^(+)PD-L1^(+)细胞频率高于对应阴性组;活化的CD4^(+)T细胞有利于CD19^(+)B细胞表面CD25的表达。结论SLE患者外周血中CD19^(+)CD25^(+)Breg降低,但细胞表面PD-1与PD-L1的表达增加,并且与相关临床表现及实验室参数存在一定的关系。活化的CD4^(+)T细胞促进Breg的分化。

Objective To investigate the expression and clinical significance of PD-1 and its ligand PD-L1 in peripheral blood CD19^(+)CD25^(+)regulatory B cells(Bregs)in patients with systemic lupus erythematosus(SLE).Methods Peripheral blood samples were collected from 50 patients and 41 healthy controls(HCs).The proportion of CD19^(+)CD25^(+)Bregs in peripheral blood as well as the expression of PD-1*B and PD-L1*B cells on CD19^(+)CD25^(+)B cells,were detected by flow cytometry.At the same time,clinical information,such as clinical manifestations and laboratory indexes,was collected from patients.CD4^(+)T cells and CD19^(+)B cells were isolated by immunomagnetic beads and co-cultured in vitro to detect the differentiation of Bregs.Results The proportion of CD19^(+)CD25^(+)Bregs in the peripheral blood of SLE patients was lower than that in HC,while the expression of PD-1 and PD-L1 on Bregs was higher than that in HCs.SLE patients with pleural effusion,arthritis,and elevated CRP had a higher frequency of Bregs compared to the corresponding negative group.SLE patients with decreased immunoglobulin M(IgM)and positive anti-ribonuclear protein(RNP)antibodies had a lower frequency of Bregs compared to the corresponding negative group.SLE patients with infection,fever,arthritis,and elevated immunoglobulin A(IgA)had a higher frequency of CD19^(+)CD25^(+)PD-1^(+)cells compared to the corresponding negative group.SLE patients with infection,fever,and elevated IgA had a higher frequency of CD19^(+)CD25^(+)PD-L1^(+)cells compared to the corresponding negative group.And activated CD4t T cells were beneficial to the expression of CD25^(+)on CD19^(+)B cells.Conclusion The peripheral blood CD19^(+)CD25^(+)Bregs are decreased in SLE patients,while the expression of PD-1 and PD-L1 on cell surface is increased,which is correlated with clinical manifestations and laboratory parameters.Activation of CD4^(+)T cells promotes the differentiation of Bregs.