SO8. Acute Rejection is Associated With Signature Donor-derived Cell Free DNA Profile Following Face Transplantation in a Rodent

PURPOSE: Acute rejection remains a significant challenge after face transplantation, which can lead to allograft loss. Noninvasive biomarkers such as donor derived cell-free DNA (ddcfDNA) have shown great promise in solid organ transplantation rejection monitoring and several studies and clinical trials have now demonstrated its clinical utility. However, within the field of vascularized composite allotransplantation very little is published on the potential of ddcfDNA for graft monitoring, as studies lack on characterizing the differential expression and genetic profile of ddcfDNA. METHODS: The authors performed face transplant on rodents and analyzed plasma and tissue at time of rejection (confirmed with histology and immunofluorescence) with subsequent cfDNA extraction and Next-Generation Sequencing. ddcfDNA was quantified and characterized on the basis of Small Nucleotide Polymorphism (SNPs) and correlated with acute rejection. RESULTS: The authors identified SNPs that match the face transplant donor animal’s DNA and not the recipient’s DNA, establishing these regions as ddcfDNA. The authors found that on average, clinical rejection was observed when the face transplanted animal’s cfDNA contains 0.31% or more of the donor cfDNA. Furthermore, the authors identified a total of 313 SNPs - mapping to 49 genes - unique to the donor genome which were consistently detected in face transplanted animals across breeds. CONCLUSION: These findings characterize a signature ddcfDNA profile associated with acute rejection after face transplantation in a rodent model. These findings are of paramount interest as potential rejection markers and may prove to be the basis for the clinical use of ddcfDNA for acute rejection monitoring.