PDF(Pubmed)
Abstract：
The molecular refinement of the diagnosis of heart allograft rejection based on whole-transcriptome analyses faces several hurdles that greatly limit its widespread clinical application. The targeted Banff Human Organ Transplant gene panel (B-HOT, including 770 genes of interest) has been developed to facilitate reproducible and cost-effective gene expression analysis of solid organ allografts. We aimed to determine in silico the ability of this targeted panel to capture the antibody-mediated rejection (AMR) molecular profile using whole-transcriptome data from 137 heart allograft biopsies (71 biopsies reflecting the entire landscape of histologic AMR, 66 non-AMR control biopsies including cellular rejection and non-rejection cases). Differential gene expression, pathway and network analyses demonstrated that the B-HOT panel captured biologically and clinically relevant genes (IFNG-inducible, NK-cells, injury, monocytes-macrophage, B-cell-related genes), pathways (interleukin and interferon signaling, neutrophil degranulation, immunoregulatory interactions, endothelial activation) and networks reflecting the pathophysiological mechanisms underlying the AMR process previously identified in whole-transcriptome analysis. Our findings support the potential clinical use of the B-HOT-gene panel as a reliable proxy to whole-transcriptome analysis for the gene expression profiling of cardiac allograft rejection.
摘要：
基于全转录组分析的心脏同种异体移植排斥诊断的分子改进面临几个障碍，这极大地限制了其广泛的临床应用。靶向班夫人器官移植基因面板(B-HOT，包括770个感兴趣的基因）已开发用于促进实体器官同种异体移植物的可重复且具有成本效益的基因表达分析。我们旨在使用来自137例心脏同种异体移植活检的全转录组数据（71例活检反映了组织学AMR的整个景观，66个非AMR对照活检，包括细胞排斥和非排斥病例）。差异基因表达，途径和网络分析表明，B-HOT面板捕获了生物学和临床相关基因(IFNG诱导的，NK细胞，损伤,单核细胞-巨噬细胞,B细胞相关基因），途径（白细胞介素和干扰素信号，中性粒细胞脱颗粒，免疫调节相互作用，内皮激活）和反映先前在全转录组分析中确定的AMR过程的病理生理机制的网络。我们的发现支持B-HOT基因组可作为心脏同种异体移植排斥反应的全转录组分析的可靠替代方法的潜在临床应用。
