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: 10515335
• 负责人: Svati H. Shah
• 金额: $ 24.15万
• 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 2024-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10515335
• 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; Heart Transplantation; Heart failure; Hour; Human; Immune; Immunogenetics; Immunophenotyping; 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; biomarker development; blood-based biomarker; 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.

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 对于美国大约 250,000 名患有终末期心力衰竭的人来说，心脏 移植（HT）仍然是金标准疗法。尽管长期生存良好，但早期死亡率 由于感染、排斥和原发性移植物功能障碍（PGD），该比例仍然很高。 PGD​​ 尤其是 HT 的破坏性并发症，其中新同种异体移植物的急性失败导致血流动力学不稳定和 终末器官灌注不足。因此，我们在此建议以有趣的初步数据为基础，表明 CLEC4C 的血浆水平，CLEC4C 是一种作为浆细胞样树突状细胞的细胞表面受体的蛋白质 (pDC) 在移植前在 HT 后进行 PGD 的患者中较高。具体来说，我们将 将免疫分析、pDC 和 PBMC 的单细胞测序以及单细胞蛋白质组学整合到 分离 pDC 以检验 pDCS 在数量和功能上富集 HT 的假设 进行 PGD 的接受者。这项研究有可能确定护理中临床相关的生物标志物 HT 接受者的研究可能有助于阐明 PGD 的潜在分子机制。