{"title":"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","authors":"Zhi Wen, Shuai Shao, Yu Feng, Zheng Wang, Jianqiang Wu, Changxue Wu, Mingwu Tian","doi":"10.1111/ctr.70286","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Introduction</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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<sup>+</sup> T cells/Th2 enrichment to prolonged QT intervals.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>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.</p>\n </section>\n </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 8","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ctr.70286","citationCount":"0","resultStr":"{\"title\":\"Altered Immune Profiles in Non-Failing Heart Donors With Induced Long QT Syndrome: A Potential Risk Factor for Cardiac Allograft Vasculopathy\",\"authors\":\"Zhi Wen, Shuai Shao, Yu Feng, Zheng Wang, Jianqiang Wu, Changxue Wu, Mingwu Tian\",\"doi\":\"10.1111/ctr.70286\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Introduction</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>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<sup>+</sup> T cells/Th2 enrichment to prolonged QT intervals.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>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.</p>\\n </section>\\n </div>\",\"PeriodicalId\":10467,\"journal\":{\"name\":\"Clinical Transplantation\",\"volume\":\"39 8\",\"pages\":\"\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2025-08-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ctr.70286\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Transplantation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/ctr.70286\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"SURGERY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Transplantation","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/ctr.70286","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"SURGERY","Score":null,"Total":0}
Altered Immune Profiles in Non-Failing Heart Donors With Induced Long QT Syndrome: A Potential Risk Factor for Cardiac Allograft Vasculopathy
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.
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.
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