Altered Immune Profiles in Non-Failing Heart Donors With Induced Long QT Syndrome: A Potential Risk Factor for Cardiac Allograft Vasculopathy

IF 1.9 4区医学 Q2 SURGERY

Clinical Transplantation Pub Date : 2025-08-22 DOI:10.1111/ctr.70286

Zhi Wen, Shuai Shao, Yu Feng, Zheng Wang, Jianqiang Wu, Changxue Wu, Mingwu Tian

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引用次数: 0

Abstract

Introduction

Cardiac allograft vasculopathy (CAV) develops more aggressively in recipients of hearts from brain-dead (BD) donors with induced long QT syndrome (iLQTS), yet the underlying mechanisms remain poorly understood. In this study, we employ a multi-omics and experimental framework to explore the role of neuro-immune interactions in non-failing donor hearts affected by iLQTS.

Methods

Single-nuclei RNA sequencing (snRNA-seq) compared four iLQTS and four non-arrhythmic non-failing donor hearts. Pathway enrichment and cell-cell communication were assessed. Plasma proteome data from BD donors and neuronal differentially expressed (DE) genes were integrated via Omicsnet. Human BD donor transcriptomes data were analyzed for immune correlation.

Results

ILQTS hearts showed elevated T/mast cells and upregulated leukocyte migration/focal adhesion pathways. Neuronal signaling (NGF, HSPG) and adhesion molecules (ITGB1, LAMININ) drove immune trafficking. Integrative proteomics identified ITGB1 as a central hub linking neuronal DE genes to BD-associated plasma proteins. Human validation linked activated CD4⁺ T cells/Th2 enrichment to prolonged QT intervals.

Conclusions

Neuro-immune dysregulation and integrin signaling related T cell activation underlie iLQTS-related heart donors. Targeting neuronal-integrin crosstalk may reduce CAV progression and improve transplant outcomes.

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诱导长QT综合征的非衰竭心脏供体免疫谱改变：异体心脏移植血管病变的潜在危险因素

同种异体心脏移植血管病变（CAV）在脑死亡（BD）供者的心脏受者中发展更积极，诱发长QT综合征（iLQTS），但其潜在机制仍知之甚少。在这项研究中，我们采用多组学和实验框架来探索受iLQTS影响的非衰竭供体心脏中神经免疫相互作用的作用。方法采用单核RNA测序（snRNA-seq）方法对4例iLQTS供体心脏和4例非心律失常供体心脏进行比较。评估通路富集和细胞间通讯。通过Omicsnet整合来自BD供体和神经元差异表达（DE）基因的血浆蛋白质组数据。对人BD供体转录组数据进行免疫相关性分析。结果ILQTS心脏显示T/肥大细胞升高，白细胞迁移/局灶黏附通路上调。神经元信号（NGF， HSPG）和粘附分子（ITGB1， LAMININ）驱动免疫运输。综合蛋白质组学鉴定ITGB1是连接神经元DE基因和bd相关血浆蛋白的中心枢纽。人类验证将活化的CD4+ T细胞/Th2富集与延长的QT间期联系起来。结论与ilqts相关的心脏供者存在神经免疫失调和整合素信号相关的T细胞激活。靶向神经元-整合素串扰可能会减少CAV的进展并改善移植结果。

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

Clinical Transplantation 医学-外科

CiteScore

3.70

自引率

4.80%

发文量

286

审稿时长

2 months

期刊介绍： Clinical Transplantation: The Journal of Clinical and Translational Research aims to serve as a channel of rapid communication for all those involved in the care of patients who require, or have had, organ or tissue transplants, including: kidney, intestine, liver, pancreas, islets, heart, heart valves, lung, bone marrow, cornea, skin, bone, and cartilage, viable or stored. Published monthly, Clinical Transplantation’s scope is focused on the complete spectrum of present transplant therapies, as well as also those that are experimental or may become possible in future. Topics include: Immunology and immunosuppression; Patient preparation; Social, ethical, and psychological issues; Complications, short- and long-term results; Artificial organs; Donation and preservation of organ and tissue; Translational studies; Advances in tissue typing; Updates on transplant pathology;. Clinical and translational studies are particularly welcome, as well as focused reviews. Full-length papers and short communications are invited. Clinical reviews are encouraged, as well as seminal papers in basic science which might lead to immediate clinical application. Prominence is regularly given to the results of cooperative surveys conducted by the organ and tissue transplant registries. Clinical Transplantation: The Journal of Clinical and Translational Research is essential reading for clinicians and researchers in the diverse field of transplantation: surgeons; clinical immunologists; cryobiologists; hematologists; gastroenterologists; hepatologists; pulmonologists; nephrologists; cardiologists; and endocrinologists. It will also be of interest to sociologists, psychologists, research workers, and to all health professionals whose combined efforts will improve the prognosis of transplant recipients.