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评价肾移植受者中新型 DSA 发展与 CXCR5+PD-1+CD8+T 细胞和 PD-1/PD-L1mRNA 表达之间的关系。

Evaluation of the relationship between de-novo DSA development and CXCR5+PD-1+CD8+ T cells and PD-1/PD-L1 mRNA expression in kidney transplant recipients.

机构信息

Department of Medical Biology and Genetics, Akdeniz University Faculty of Medicine, Antalya, Turkey.

Division of Nephrology, Department of Internal Medicine, Akdeniz University Faculty of Medicine, Antalya, Turkey.

出版信息

Clin Transplant. 2023 Nov;37(11):e15104. doi: 10.1111/ctr.15104. Epub 2023 Aug 17.

Abstract

BACKGROUND AND AIMS

The relationship between the Follicular Cytotoxic T cell subgroup and expression levels of PD1/PD-L1 genes and the development of donor specific antibody (DSA) is unknown. In this study, we aimed to examine CD8+CXCR5+PD-1+ follicular cytotoxic T cell levels and expression levels of PD1/PD-L1 genes in peripheral blood lymphocytes in de-novo DSA positive and negative kidney transplant recipients (KTR).

METHODS

In our study, expression of PD-1/ PD-L1 genes by Real-Time Quantitative PCR method and CD8+CXCR5+PD-1+ T cell expression levels by flow cytometric method were obtained from peripheral blood samples. 63 participants were included in the study (de-novo DSA positive recipients (n = 22, group 1), de-novo DSA negative recipients (n = 20, group 2) and healthy control (n = 21, group 3). All patients had negative PRA before kidney transplantation. Expression (%) levels of target cells were evaluated by flow cytometry method. IBM SPSS Statistics for Windows Version 22 and R.3.3.2 software were used to evaluate the data.

RESULTS

The demographic data of the groups were similar. PD-1 mRNA expression was higher in de-novo DSA positive KTR than negative (respectively, 1.03 ± .29/.82 ± .15, p: .001). CD8+CXCR5+PD-1+ T cell expression levels were found to be higher in the de-novo DSA positive group than in the negative group and similar to the healthy group (respectively, 3.06 ± 1.98/.52 ± .40, p:.001, 3.06 ± 1.98/2.78 ± .59, p:.62). The percentage of CD8+CXCR5+PD-1+ expressing T cells was significantly lower in the HLA-Class II+ group than other groups (HLA CI/II/ I+II, respectively, 3.63 ± 2.72/1.65 ± .50/3.68 ± 1.67, p: .04).

CONCLUSIONS

In our study, a significant relationship was found between DSA formation and PD-1 mRNA level and CD8+CXCR5+PD-1+ follicular cytotoxic T cell in KTR.

摘要

背景与目的

滤泡细胞毒性 T 细胞亚群与 PD1/PD-L1 基因的表达水平以及供体特异性抗体(DSA)的发展之间的关系尚不清楚。本研究旨在检测初发 DSA 阳性和阴性肾移植受者(KTR)外周血淋巴细胞中 CD8+CXCR5+PD-1+滤泡细胞毒性 T 细胞水平和 PD1/PD-L1 基因的表达水平。

方法

本研究通过实时定量 PCR 方法检测 PD-1/PD-L1 基因的表达,通过流式细胞术检测 CD8+CXCR5+PD-1+T 细胞的表达水平。共纳入 63 例患者(初发 DSA 阳性受者(n=22,第 1 组)、初发 DSA 阴性受者(n=20,第 2 组)和健康对照组(n=21,第 3 组)。所有患者在肾移植前 PRA 均为阴性。通过流式细胞术评估靶细胞的表达(%)水平。采用 IBM SPSS Statistics for Windows Version 22 和 R.3.3.2 软件对数据进行评估。

结果

各组的人口统计学数据相似。与阴性组相比,初发 DSA 阳性 KTR 的 PD-1mRNA 表达更高(分别为 1.03±0.29/0.82±0.15,p:0.001)。初发 DSA 阳性组的 CD8+CXCR5+PD-1+T 细胞表达水平高于阴性组,与健康组相似(分别为 3.06±1.98/0.52±0.40,p:0.001,3.06±1.98/2.78±0.59,p:0.62)。与其他组相比,HLA-Class II+组的 CD8+CXCR5+PD-1+表达 T 细胞的百分比明显更低(HLA CI/II/ I+II,分别为 3.63±2.72/1.65±0.50/3.68±1.67,p:0.04)。

结论

在本研究中,我们发现 KTR 中 DSA 形成与 PD-1mRNA 水平和 CD8+CXCR5+PD-1+滤泡细胞毒性 T 细胞之间存在显著关系。

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