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接受不同诱导治疗的肺移植患者的血清蛋白质组学分析。

Serum proteomics analysis of lung transplant patients receiving different induction therapies.

作者信息

Nasrollahi-Shirazi Shahrooz, Unterwurzacher Markus, Berezhinskiy Hatice Oya, Alemanno Sophia, Hoetzenecker Konrad, Aigner Clemens, Jaksch Peter, Mohr Thomas, Kratochwill Klaus, Benazzo Alberto

机构信息

Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria.

Comprehensive Center for Chest Diseases (CCCD), Medical University of Vienna, Vienna, Austria.

出版信息

Front Immunol. 2025 Aug 28;16:1616781. doi: 10.3389/fimmu.2025.1616781. eCollection 2025.

DOI:10.3389/fimmu.2025.1616781
PMID:40948797
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12422901/
Abstract

INTRODUCTION

Induction therapy is widely used in lung transplantation to control the host alloresponse, reducing acute cellular rejection and improving graft survival. Despite its use, data on the biological effects of different induction agents remain limited.

METHODS

This study examines serum proteomics profiles in lung transplant patients receiving alemtuzumab, anti-thymocyte globulin (ATG), or no induction therapy. Adult lung transplant recipients who underwent transplantation between 2007 and 2013 at the Medical University of Vienna were included. Using mass spectrometry (MS), serum samples were examined before transplantation (T1) and 12 months post-transplant (T2).

RESULTS

Among 102 patients (50 alemtuzumab, 34 ATG, 18 no induction), we identified significantly differentially expressed proteins over time and between groups at T2. In the alemtuzumab group, 40 proteins were differentially expressed (3 upregulated, 37 downregulated), in ATG, 22 proteins (3 upregulated, 19 downregulated), and none in the no-induction group. At T2, two proteins (fibulin-1 and fetuin-B) were downregulated between alemtuzumab and no induction, with no significant differences between alemtuzumab and ATG or ATG and no induction.

DISCUSSION

Our findings suggest alemtuzumab may have a stronger effect on circulating proteome. Further studies are warranted to elucidate the underlying mechanisms and explore potential clinical implications.

摘要

引言

诱导疗法在肺移植中被广泛用于控制宿主同种异体反应,减少急性细胞排斥反应并提高移植物存活率。尽管使用了诱导疗法,但关于不同诱导剂生物学效应的数据仍然有限。

方法

本研究检测了接受阿仑单抗、抗胸腺细胞球蛋白(ATG)或未接受诱导疗法的肺移植患者的血清蛋白质组学图谱。纳入了2007年至2013年在维也纳医科大学接受移植的成年肺移植受者。使用质谱法(MS)在移植前(T1)和移植后12个月(T2)检测血清样本。

结果

在102例患者中(50例接受阿仑单抗,34例接受ATG,18例未接受诱导疗法),我们发现在T2时随时间推移以及组间存在显著差异表达的蛋白质。在阿仑单抗组中,有40种蛋白质差异表达(3种上调,37种下调),在ATG组中有22种蛋白质(3种上调,19种下调),而未接受诱导疗法的组中无差异表达。在T2时,阿仑单抗组与未接受诱导疗法组之间有两种蛋白质(纤连蛋白-1和胎球蛋白-B)下调,阿仑单抗组与ATG组之间或ATG组与未接受诱导疗法组之间无显著差异。

讨论

我们的研究结果表明阿仑单抗可能对循环蛋白质组有更强的作用。有必要进一步研究以阐明其潜在机制并探索潜在的临床意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d913/12422901/b9238a6bfd8f/fimmu-16-1616781-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d913/12422901/004410792195/fimmu-16-1616781-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d913/12422901/b9238a6bfd8f/fimmu-16-1616781-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d913/12422901/004410792195/fimmu-16-1616781-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d913/12422901/b9238a6bfd8f/fimmu-16-1616781-g002.jpg

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本文引用的文献

1
Fetuin B Is Related to Cytokine/Chemokine and Insulin Signaling in Adipose Tissue and Plasma in Humans.胎球蛋白B与人类脂肪组织和血浆中的细胞因子/趋化因子及胰岛素信号传导相关。
J Clin Endocrinol Metab. 2025 Sep 16;110(10):e3235-e3244. doi: 10.1210/clinem/dgaf073.
2
Longitudinal Fluctuations in Protein Concentrations and Higher-Order Structures in the Plasma Proteome of Kidney Failure Patients Subjected to a Kidney Transplant.肾衰竭患者接受肾移植后血浆蛋白质组中蛋白质浓度和高级结构的纵向波动。
J Proteome Res. 2024 Jun 7;23(6):2124-2136. doi: 10.1021/acs.jproteome.4c00064. Epub 2024 May 3.
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Fetuin B in white adipose tissue induces inflammation and is associated with peripheral insulin resistance in mice and humans.
白色脂肪组织中的胎球蛋白 B 可诱导炎症反应,并与小鼠和人类外周胰岛素抵抗相关。
Obesity (Silver Spring). 2024 Mar;32(3):517-527. doi: 10.1002/oby.23961. Epub 2023 Dec 19.
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Proteomic analysis investigating kidney transplantation outcomes- a scoping review.蛋白质组学分析探讨肾移植结局-范围综述。
BMC Nephrol. 2023 Nov 22;24(1):346. doi: 10.1186/s12882-023-03401-0.
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Fetuin-B Overexpression Promotes Inflammation in Diabetic Retinopathy Through Activating Microglia and the NF-κB Signaling Pathway.胎球蛋白-B 过表达通过激活小胶质细胞和 NF-κB 信号通路促进糖尿病视网膜病变中的炎症反应。
Curr Eye Res. 2024 Feb;49(2):168-179. doi: 10.1080/02713683.2023.2276683. Epub 2024 Jan 18.
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Evaluating anti-thymocyte globulin induction doses for better allograft and patient survival in Asian kidney transplant recipients.评估抗胸腺细胞球蛋白诱导剂量以改善亚洲肾移植受者的移植物和患者存活率。
Sci Rep. 2023 Aug 2;13(1):12560. doi: 10.1038/s41598-023-39353-6.
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Contribution of Proteomics in Transplantation: Identification of Injury and Rejection Markers.蛋白质组学在移植中的贡献:损伤和排斥标志物的鉴定。
Transplantation. 2023 Oct 1;107(10):2143-2154. doi: 10.1097/TP.0000000000004542. Epub 2023 Feb 23.
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Diverse functions of apolipoprotein A-I in lung fibrosis.载脂蛋白 A-I 在肺纤维化中的多种功能。
Am J Physiol Cell Physiol. 2023 Feb 1;324(2):C438-C446. doi: 10.1152/ajpcell.00491.2022. Epub 2022 Dec 19.
9
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10
The ApoA-I mimetic peptide 4F attenuates in vitro replication of SARS-CoV-2, associated apoptosis, oxidative stress and inflammation in epithelial cells.载脂蛋白 A-I 模拟肽 4F 可抑制 SARS-CoV-2 在体外的复制,以及相关的上皮细胞凋亡、氧化应激和炎症反应。
Virulence. 2021 Dec;12(1):2214-2227. doi: 10.1080/21505594.2021.1964329.