Background

Programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1)-targeted therapies have enhanced T-cell response and demonstrated efficacy in the treatment of multiple cancers. However, the role and clinical significance of PD-L1 expression on CD19⁺ B-cells and their subsets, with particular reference to systemic lupus erythematosus (SLE), have not yet been studied in detail.

Objective

The present study aimed to investigate PD-L1 expression on CD19+ B-cells and their subsets, in addition to exploring its possible role in Tfh-cell activation and B-cell differentiation in SLE.

Methods

Frequencies of CD19⁺ B-cells, their subsets, PD-L1 and Tfh cells in the peripheral blood of SLE patients and healthy controls (HCs) were determined using cytometry. The clinical data of SLE patients were recorded in detail, and the correlation between their laboratory parameters, clinical parameters and disease activity indices was statistically analyzed. CD19⁺PD-L1⁺B-cells and CD19⁺PD-L1⁻ B-cells were sorted and cultured with a stimulant, following which the supernatants were collected for immunoglobulin G and anti-double stranded DNA detection via enzyme-linked immunosorbent assay.

Results

In SLE patients, CD19⁺B-cells and partial subgroups were enriched in peripheral blood. Also, the observed increase in the frequency of CD19⁺PD-L1⁺B-cells was significantly associated with a higher disease activity index. An in vitro culture test demonstrated that the amounts of anti-dsDNA and immunoglobulin G secreted by the CD19⁺PD-L1⁺B-cells of SLE patients and HCs were vastly different. In addition, a strong correlation existed between the frequencies of CD19⁺PD-L1⁺B-cells and defined Tfh cells of SLE patients.

Conclusion

This study demonstrated that the expression of CD19⁺PD-L1⁺B-cells in the peripheral blood of SLE patients was abnormal, and that disease-related laboratory parameters and clinical indicators were correlated. CD19⁺PD-L1⁺B-cells were enriched and played a critical role in activating the pathogenic T-cell and B-cell responses in patients with SLE.

中文翻译：

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系统性红斑狼疮CD19 ⁺ B细胞及其亚群表达的程序性细胞死亡配体1的作用和临床意义

背景

以编程性细胞死亡1（PD-1）和编程性死亡配体1（PD-L1）为靶标的疗法增强了T细胞反应，并证明了其在治疗多种癌症中的功效。然而，尚未详细研究PD-L1在CD19 ⁺ B细胞及其亚群上的作用和临床意义，特别是针对系统性红斑狼疮（SLE）。

客观的

本研究旨在研究CD19 + B细胞及其亚组上PD-L1的表达，并探讨其在SLE中Tfh细胞激活和B细胞分化中的可能作用。

方法

使用细胞计数法测定SLE患者和健康对照（HCs）外周血中CD19 ⁺ B细胞，其亚群，PD-L1和Tfh细胞的频率。详细记录SLE患者的临床资料，并统计分析他们的实验室参数，临床参数与疾病活动性指标之间的相关性。分选CD19 ⁺ PD-L1 ⁺ B细胞和CD19 ⁺ PD-L1 ^- B细胞，并用刺激物培养，然后收集上清液用于免疫球蛋白G和通过酶联免疫吸附法检测抗双链DNA。

结果

在SLE患者中，外周血中富含CD19 ⁺ B细胞和部分亚组。而且，观察到的CD19 ⁺ PD-L1 ⁺ B细胞频率的增加与更高的疾病活动指数显着相关。体外培养试验表明，SLE患者和HCs的CD19 ⁺ PD-L1 ⁺ B细胞分泌的抗dsDNA和免疫球蛋白G的量存在很大差异。另外，SLE患者的CD19 ⁺ PD-L1 ⁺ B细胞的频率与确定的Tfh细胞之间存在强烈的相关性。

结论

该研究表明，SLE患者外周血CD19 ⁺ PD-L1 ⁺ B细胞表达异常，与疾病相关的实验室指标和临床指标相关。CD19 ⁺ PD-L1 ⁺ B细胞富集并在激活SLE患者的病原性T细胞和B细胞反应中起关键作用。