Exploring donor-derived cell-free DNA as a rejection biomarker during uterus transplant follow up

Uterus transplantation (UTx) is a treatment option for women with absolute uterine factor infertility who wish to become pregnant and have a healthy live birth. Tissue biopsy is the gold standard for diagnosing allograft rejection. Circulating donor-derived cell-free DNA (dd-cfDNA) has recently emerged as a non-invasive biomarker with strong predictive value for rejection in solid organ transplants. dd-cfDNA quantification by next-generation sequencing (NGS) was evaluated in two UTx patients from transplantation to childbirth. The results were compared with cervical biopsies. Additionally, capillary electrophoresis was used to characterize cfDNA fragmentation pattern. dd-cfDNA levels significantly increase during biopsy-proven rejection episodes (0.39% vs 0.17% in patient 1 and 0.34% vs 0.26% in patient 2). Additionally, cfDNA fragment analysis shows an elevation of high molecular weight cfDNA fragments during rejection. These findings support dd-cfDNA as a promising non-invasive tool for monitoring UTx rejection. Future studies should focus on characterizing dd-cfDNA kinetics and cfDNA fragmentomics in larger cohorts to optimize rejection detection and improve patient outcomes. Uterus transplantation (UTx) is a treatment option for women without a functioning uterus that want to become pregnant. Analyzing small parts of the transplanted uterus using a biopsy from the cervix allows follow up to check transplantation has been successful. Genetic material is released by transplanted organs and circulates in the blood (dd-cfDNA). This can be used to detect rejection following kidney and heart transplantation. We evaluated whether the dd-cfDNA could be used in two people who had uterus transplants. We took regular blood samples following transplantation until childbirth and quantified the dd-cfDNA. We compared these results with samples taken from their cervix. We found that dd-cfDNA levels significantly increase during rejection. Our results suggest that dd-cfDNA could be used as a non-invasive tool for monitoring uterus transplant rejection. Gonzállez-Roca, Rius et al. investigate whether donor-derived cell-free DNA (dd-cfDNA) can be a biomarker in the follow up of patients with uterus transplant. The results indicate that dd-cfDNA is significantly increased when a rejection is diagnosed, as well as fragments above 400 base pairs.