Transcript analysis of uterus transplant cervical biopsies using the Banff Human Organ Transplant panel

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.