比较 FOXP3 和白细胞介素 35 在具有优异长期移植物功能和急性排斥反应的肾移植受者中的表达谱。

Comparison of FOXP3 and Interleukin 35 Expression Profiles in Kidney Transplant Recipients With Excellent Long-Term Graft Function and Acute Rejection.

机构信息

From the Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Exp Clin Transplant. 2021 Nov;19(11):1142-1148. doi: 10.6002/ect.2021.0116.

DOI:10.6002/ect.2021.0116

PMID:34812705

Abstract

OBJECTIVES

Transplant tolerance is defined as graft acceptance without long-term use of immunosuppressive agents. Regulatory T cells are involved in the maintenance of peripheral self-tolerance by actively suppressing the activation and expansion of autoreactive T cells. In the present study, we compared the expression profiles of forkhead box protein P3 (FOXP3) and interleukin 35 in kidney transplant recipients who had excellent long-term graft function under immunosuppression versus recipients who had acute rejection.

MATERIALS AND METHODS

The 40 kidney transplant recipients included in this study were divided into 2 groups: 27 recipients with excellent long-term graft function and 13 recipients with acute rejection. After collection of whole peripheral blood, peripheral blood mononuclear cells were isolated from the blood samples. After RNAextraction and cDNAsynthesis from each collected sample, expression levels of interleukin 35 and FOXP3 were determined using in-house SYBER green-based real-time polymerase chain reaction. We used t tests to analyze data.

RESULTS

Mean ages of recipients with excellent longterm graft function and recipients with acute rejection were 42.1 and 45.5 years, respectively. We found that FOXP3 and interleukin 35 expression levels were significantly increased in recipients with excellentlongterm graftfunction comparedwith recipientswith acute rejection. FOXP3 expression levels were significantly higher in those with excellent long-term graft function with graft survivalrate of <10 years,whereas interleukin 35 expression levels were significantly higher in patients with graft survival rate >10 years (P < .05). Expression levels of FOXP3 and interleukin 35 were greater in those from 35 to 50 years old versus with those in the other age ranges.

CONCLUSIONS

Expression patterns of FOXP3 and interleukin 35 may have the potential to be used as prognostic biomarkers for kidney transplant outcomes.

摘要

目的

移植耐受被定义为在不长期使用免疫抑制剂的情况下接受移植物。调节性 T 细胞通过主动抑制自身反应性 T 细胞的激活和扩增，参与外周自身耐受的维持。在本研究中，我们比较了在免疫抑制下具有优异长期移植物功能的肾移植受者与发生急性排斥反应的受者的叉头框蛋白 P3（FOXP3）和白细胞介素 35 的表达谱。

材料和方法

本研究纳入的 40 例肾移植受者分为 2 组：27 例长期移植物功能良好的受者和 13 例发生急性排斥反应的受者。采集全血后，从血液样本中分离外周血单个核细胞。从每个采集的样本中提取 RNA 并合成 cDNA 后，使用内部 SYBER 绿色实时聚合酶链反应测定白细胞介素 35 和 FOXP3 的表达水平。我们使用 t 检验分析数据。

结果

长期移植物功能良好的受者和急性排斥反应的受者的平均年龄分别为 42.1 岁和 45.5 岁。我们发现，长期移植物功能良好的受者中 FOXP3 和白细胞介素 35 的表达水平明显高于急性排斥反应的受者。具有<10 年移植存活率的长期移植物功能良好的患者中 FOXP3 表达水平显著升高，而>10 年移植存活率的患者中白细胞介素 35 表达水平显著升高（P<0.05）。FOXP3 和白细胞介素 35 的表达水平在 35 至 50 岁之间的患者中显著高于其他年龄组。