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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.