Screening of novel biomarkers for acute kidney transplant rejection using DIA-MS based proteomics.

IF 2.1 4区生物学 Q3 BIOCHEMICAL RESEARCH METHODS

PROTEOMICS – Clinical Applications Pub Date : 2024-05-01 Epub Date: 2024-01-12 DOI:10.1002/prca.202300047

Ce Wang, Gang Feng, Jie Zhao, Yang Xu, Yang Li, Lin Wang, Meng Wang, Miao Liu, Yilin Wang, Hong Mu, Chunlei Zhou

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Abstract

Background: Kidney transplantation is the preferred treatment for patients with end-stage renal disease. However, acute rejection poses a threat to the graft long-term survival. The aim of this study was to identify novel biomarkers to detect acute kidney transplant rejection.

Methods: The serum proteomic profiling of kidney transplant patients with T cell-mediated acute rejection (TCMR) and stable allograft function (STA) was analyzed using data-independent acquisition mass spectrometry (DIA-MS). The differentially expressed proteins (DEPs) of interest were further verified by enzyme-linked immunosorbent assay (ELISA).

Results: A total of 131 DEPs were identified between STA and TCMR patients, 114 DEPs were identified between mild and severe TCMR patients. The verification results showed that remarkable higher concentrations of serum amyloid A protein 1 (SAA1) and insulin like growth factor binding protein 2 (IGFBP2), and lower fetuin-A (AHSG) concentration were found in TCMR patients when compared with STA patients. We also found higher SAA1 concentration in severe TCMR group when compared with mild TCMR group. The receiver operating characteristics (ROC) analysis further confirmed that combination of SAA1, AHSG, and IGFBP2 had excellent performance in the acute rejection diagnosis.

Conclusions: Our data demonstrated that serum SAA1, AHSG, and IGFBP2 could be effective biomarkers for diagnosing acute rejection after kidney transplantation. DIA-MS has great potential in biomarker screening of kidney transplantation.

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利用基于 DIA-MS 的蛋白质组学筛选急性肾移植排斥反应的新型生物标志物。

背景：肾移植是终末期肾病患者的首选治疗方法。然而，急性排斥反应对移植肾的长期存活构成威胁。本研究旨在确定检测急性肾移植排斥反应的新型生物标志物：方法：使用数据无关采集质谱（DIA-MS）分析了T细胞介导的急性排斥反应（TCMR）和异体移植功能稳定（STA）的肾移植患者的血清蛋白质组图谱。通过酶联免疫吸附试验（ELISA）进一步验证了感兴趣的差异表达蛋白（DEPs）：结果：在 STA 和 TCMR 患者之间共鉴定出 131 个 DEPs，在轻度和重度 TCMR 患者之间鉴定出 114 个 DEPs。验证结果显示，与 STA 患者相比，TCMR 患者的血清淀粉样蛋白 A 蛋白 1（SAA1）和胰岛素样生长因子结合蛋白 2（IGFBP2）浓度明显较高，而胎儿素-A（AHSG）浓度较低。我们还发现，与轻度 TCMR 组相比，重度 TCMR 组的 SAA1 浓度更高。接受者操作特征（ROC）分析进一步证实，SAA1、AHSG和IGFBP2的组合在急性排斥反应诊断中表现优异：我们的数据表明，血清 SAA1、AHSG 和 IGFBP2 可作为诊断肾移植术后急性排斥反应的有效生物标志物。DIA-MS在肾移植的生物标志物筛选中具有巨大潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

PROTEOMICS – Clinical Applications 医学-生化研究方法

CiteScore

5.20

自引率

5.00%

发文量

审稿时长

1 months

期刊介绍： PROTEOMICS - Clinical Applications has developed into a key source of information in the field of applying proteomics to the study of human disease and translation to the clinic. With 12 issues per year, the journal will publish papers in all relevant areas including: -basic proteomic research designed to further understand the molecular mechanisms underlying dysfunction in human disease -the results of proteomic studies dedicated to the discovery and validation of diagnostic and prognostic disease biomarkers -the use of proteomics for the discovery of novel drug targets -the application of proteomics in the drug development pipeline -the use of proteomics as a component of clinical trials.