Immunogenetic Profiling for Risk of Primary Graft Dysfunction after Heart Transplantation

心脏移植后原发性移植物功能障碍风险的免疫遗传学分析

• 批准号: 10391731
• 负责人: Svati H. Shah
• 金额: $ 20.13万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-11-01 至 2023-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10391731
• 关键词: Acute; Affect; Agonist; Allografting; Biological Markers; Blood specimen; Cardiotoxicity; Caring; Cell Surface Receptors; Cells; Cellular biology; Clinical; Data; Dendritic Cells; Event; Failure; Functional disorder; Future; Gene Expression; Genes; Goals; Gold; Heart Transplantation; Heart failure; Hour; Human; Immune; Immunogenetics; Immunosuppression; Incidence; Infection; Inflammatory; Infrastructure; Interferons; Intubation; Mediating; Membrane Proteins; Modeling; Molecular; Morbidity - disease rate; Myelogenous; Myocardial dysfunction; Organ; Organ Preservation; Organ Procurements; Outcome; Pathway interactions; Patients; Peripheral Blood Mononuclear Cell; Persons; Phenotype; Plasma; Population; Production; Proteins; Proteomics; Risk; Risk Factors; Role; Serum; Signal Transduction; Surface; TLR9 gene; Techniques; Testing; Time; Toll-like receptors; Transplant Recipients; Transplantation; Transplanted Heart Complication; United States; Validation; Work; base; biomarker development; blood-based biomarker; case control; cell free DNA; cell type; clinical risk; clinically relevant; cohort; cytokine; disorder risk; graft dysfunction; hemodynamics; high risk; hypoperfusion; infection risk; ischemic injury; mortality; mortality risk; novel; novel marker; patient biomarkers; precision medicine; response; single cell sequencing; single-cell RNA sequencing; specific biomarkers; transcriptomics; transplant centers

Immunogenetic Profiling for Risk of Primary Graft Dysfunction after Heart Transplantation For the approximately 250,000 people in the United States living with end-stage heart failure, heart transplantation (HT) remains the gold standard therapy. Despite excellent long-term survival, early mortality remains high as a result of infection, rejection, and primary graft dysfunction (PGD). PGD, in particular, is a devastating complication of HT in which acute failure of the new allograft leads to hemodynamic instability and end-organ hypoperfusion. Thus, we propose herein to build upon interesting preliminary data suggesting that plasma levels of CLEC4C, a protein that serves as a cell surface receptor for plasmacytoid dendritic cells (pDCs), are higher prior to transplant in patients who subsequently develop PGD after HT. Specifically, we will integrate immune profiling, single cell sequencing of pDCs and PBMCs, and single cell proteomics in isolated pDCs to test the hypothesis that pDCS are quantitatively and functionally enriched in HT recipient who develop PGD. This study has the potential to identify clinically relevant biomarkers in the care of HT recipients and may help to elucidate the underlying molecular mechanisms of PGD.

免疫遗传分析，用于心脏移植后原发性移植功能障碍的风险 对于美国大约25万人患有最终心力衰竭的人 移植（HT）仍然是黄金标准疗法。尽管长期生存良好，但早期死亡率 由于感染，排斥和原发性移植功能障碍（PGD）仍然很高。特别是PGD是 HT的毁灭性并发症，其中新同种异体移植的急性衰竭导致血流动力学不稳定和 最终器官灌注。因此，我们在此提议以有趣的初步数据为基础 CLEC4C的血浆水平，一种蛋白质，用作细胞表面受体的浆细胞类动物树突状细胞 （PDC）在移植前较高，在HT后随后发展PGD的患者。具体来说，我们会的 整合免疫分析，PDC和PBMC的单细胞测序以及单细胞蛋白质组学 分离的PDC测试了PDC在数量上且功能丰富HT的假设 发展PGD的接受者。这项研究有可能识别护理中临床相关的生物标志物 HT接受者的含量，可能有助于阐明PGD的基本分子机制。