Exploratory Biomarkers for Acute Rejection in Vascularized Composite Allotransplantation

Vascularized composite allotransplantation (VCA) involves immunologically heterogeneous tissues and is associated with high rates of acute rejection (AR), particularly due to the immunogenicity of the skin. This study assessed biomarkers to monitor AR in a recipient of full-face and bilateral hand transplantation. Over 4.6 years postoperatively, we analyzed serial blood and tissue samples, including donor-derived cell-free DNA (dd-cfDNA) in plasma, recipient DNA in allograft biopsies using short tandem repeat (STR) analysis, lymphocyte subsets via flow cytometry, and level of angiotensin II type 1 receptor antibodies (AT1R-Abs). dd-cfDNA and STR showed trends toward elevated recipient signal during acute rejection, though differences were not statistically significant. CD8+ T-cell percentages increased before AR onset, suggesting potential as a prognostic biomarker. AT1R-Ab levels did not differ significantly between AR and non-rejection episodes, possibly due to prophylactic immune cell depletion. While dd-cfDNA and STR levels correlate with rejection episodes and reflect key cellular events within graft tissue, CD8+ T-cell count remains the most robust prognostic biomarker for predicting the onset of cytotoxicity in this patient. These findings highlight the importance of further longitudinal, multi-patient studies to validate emerging biomarkers and improve rejection monitoring strategies in VCA.