Broecker Verena, Toulza Frederic, Brännström Mats, Ernst Angela, Roufosse Candice, Carbonnel Marie, Alkattan Zeinab, Mölne Johan
Department of Clinical Pathology, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden; Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
Department of Immunology and Inflammation, Imperial College, Centre for Inflammatory Disease, London, United Kingdom.
Am J Transplant. 2025 Feb;25(2):329-342. doi: 10.1016/j.ajt.2024.08.027. Epub 2024 Aug 30.
Uterus transplantation is being more widely implemented in clinical practice. Monitoring of rejection is routinely done for cervical biopsies and is dependent on histopathological assessment, as rejections are clinically silent and nonhistological biomarkers are missing. Until this gap is filled, it is important to corroborate the histopathological diagnosis of rejection through independent methods such as gene expression analysis. In this study, we compared our previously published scoring system for grading rejection in uterus transplant cervical biopsies to the gene expression profile in the same biopsy. For this, we used the Banff Human Organ Transplant gene panel to analyze the expression of 788 genes in 75 paraffin-embedded transplant cervical biopsies with a spectrum of histologic findings, as well as in 24 cervical biopsies from healthy controls. We found that gene expression in borderline changes did not differ from normal transplants, whereas the genes with increased expression in mild rejections overlapped with previously published rejection-associated transcripts. Moderate/severe rejection samples showed a gene expression pattern characterized by a mixture of rejection-associated and tissue injury-associated genes and a decrease in epithelial transcripts. In summary, our findings support our proposed scoring system for rejection but argue against the treatment of borderline changes.
子宫移植在临床实践中的应用越来越广泛。对宫颈活检进行排斥反应监测是常规操作，且依赖于组织病理学评估，因为排斥反应在临床上没有症状，也缺乏非组织学生物标志物。在填补这一空白之前，通过基因表达分析等独立方法来证实排斥反应的组织病理学诊断非常重要。在本研究中，我们将之前发表的子宫移植宫颈活检排斥反应分级评分系统与同一活检样本的基因表达谱进行了比较。为此，我们使用班夫人类器官移植基因面板，分析了75例具有一系列组织学表现的石蜡包埋移植宫颈活检样本以及24例健康对照宫颈活检样本中788个基因的表达情况。我们发现，临界变化中的基因表达与正常移植样本没有差异，而轻度排斥反应中表达增加的基因与之前发表的与排斥反应相关的转录本重叠。中重度排斥反应样本显示出一种基因表达模式，其特征是与排斥反应相关的基因和与组织损伤相关的基因混合存在，且上皮转录本减少。总之，我们的研究结果支持我们提出的排斥反应评分系统，但不支持对临界变化进行治疗。
