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特发性膜性肾病患者外周血 T 细胞和髓源抑制细胞的多样性。

The diversity of peripheral blood T cells and myeloid-derived suppressor cells in patients with idiopathic membranous nephropathy.

出版信息

Clin Nephrol. 2024 Jun;101(6):287-297. doi: 10.5414/CN111059.

DOI:10.5414/CN111059
PMID:38511675
Abstract

OBJECTIVE

Membranous nephropathy is a leading cause of adult-onset nephrotic syndrome. Peripheral T cells and myeloid-derived suppressor cells (MDSCs) are closely associated with autoimmune diseases, while their exact roles and interaction in these processes are unclear. Here, we studied the roles of T cells, MDSCs, and their subsets in patients with idiopathic membranous nephropathy (IMN).

MATERIALS AND METHODS

35 IMN patients and 30 healthy controls were included in this retrospective study. Flow cytometry was performed to determine the phenotype of human T cells and MDSCs in peripheral blood mononuclear cells (PBMCs). Anti-PLA2R was measured by ELISA. Values ≥ 20 RU/mL were defined as positive and < 14 RU/mL as negative.

RESULTS

A higher ratio of CD4/CD8 T cells with a lower proportion of Tregs, a remarkably lower proportion of G-MDSCs (but not M-MDSCs), lower frequency of PD-L2+G-MDSCs, and higher frequency of PD-L1+M-MDSCs were found in IMN patients compared to healthy controls. The ratio of CD4/CD8 T cells was higher, and the frequencies of PD-1+CD4+ T cells, CTLA-4+CD4+ T cells, PD-1+Tregs, and CTLA-4+Tregs were lower in PBMCs of PLA2R-positive IMN patients compared to PLA2R-negative IMN patients.

CONCLUSION

Tregs and G-MDSCs were reduced in the circulation of the IMN patients, which may promote understanding of the crucial functions that are mediated by these cells in the pathogenesis of IMN.

摘要

目的

膜性肾病是成人肾病综合征的主要病因。外周 T 细胞和髓系来源抑制细胞(MDSC)与自身免疫性疾病密切相关,但其在这些过程中的确切作用和相互作用尚不清楚。在这里,我们研究了 T 细胞、MDSC 及其亚群在特发性膜性肾病(IMN)患者中的作用。

材料和方法

本回顾性研究纳入了 35 名 IMN 患者和 30 名健康对照者。采用流式细胞术检测外周血单个核细胞(PBMCs)中人类 T 细胞和 MDSC 的表型。采用 ELISA 法检测抗 PLA2R 抗体。≥20 RU/mL 定义为阳性,<14 RU/mL 定义为阴性。

结果

与健康对照组相比,IMN 患者的 CD4/CD8 T 细胞比值较高,Tregs 的比例较低,G-MDSC(而非 M-MDSC)的比例明显较低,PD-L2+G-MDSC 的频率较低,PD-L1+M-MDSC 的频率较高。与 PLA2R 阴性 IMN 患者相比,PLA2R 阳性 IMN 患者的 CD4/CD8 T 细胞比值更高,PD-1+CD4+T 细胞、CTLA-4+CD4+T 细胞、PD-1+Tregs 和 CTLA-4+Tregs 的频率更低。

结论

IMN 患者循环中的 Tregs 和 G-MDSC 减少,这可能有助于理解这些细胞在 IMN 发病机制中的关键作用。

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