DNA released from rejecting organs is an indicator of the degree of graft cellular damage

Abstract

Warm and cold ischemia as well as rejection of the transplanted organ or tissue cause destructive changes in the graft parenchyma. Fragments of disintegrated cellular organelles are phagocytized and digested by recipient scavenger cells in lymph nodes, spleen, and liver. Some fragments engulfed by dendritic cells are processed including donor DNA present in the ingested cellular debris. The question arises as to whether the DNA from the disintegrated cells may be used as a measure of graft damage. In this study we provide evidence that both syngeneic and allogeneic organ transplantation followed by “seeding” of donor DNA from graft cells is internalized in recipient macrophages and dendritic cells in lymphoid organs. The kinetics of accumulation of donor DNA in recipient tissues reflected the degree of ischemic and immune graft damage. Immunosuppression with cyclosporine or tacrolimus did not significantly attenuate the DNA release. Measurements of the concentration of donor DNA gives insight into the kinetics of allograft rejection. Real-time polymerase chain reaction for donor DNA in recipient serum and blood leukocytes that have engulfed donor cell debris may be useful for clinical diagnostic application.