Aim: Antibody mediated rejection (AMR) remains one of the major challenges for long-term survival following heart transplantation. The immediate and long-term impact of HLA antibodies on graft survival is well established. Our previous data indicated reduction of epidermal growth factor (EGF) levels in heart transplant recipients with AMR. The role of EGF in inducing allograft injury is previously demonstrated by others and the use of EGFR tyrosine kinase inhibitor reduced the chronic rejection changes in kidney transplant model.
Methods: Combined with our early data indicating serum EGF reduction associated with AMR in heart transplant patients, we studied the impact of EGF in a murine BALB/c to C57B6 heart transplant model.
Results: Treatment with recombinant EGF shortened the heart allograft survival at day 7 post-transplant compared to the vehicle treated controls. To expand upon our prior observations regarding the reduction of serum EGF associated with AMR in heart transplant patients, we explored the influence of EGF in a murine BALB/c to C57B6 heart transplant model. Administration of recombinant EGF led to lower palpation score of heart allografts compared to vehicle-treated controls at day 7 post-transplantation.
Conclusion: Our preliminary data might support the potential involvement of EGF in allograft injury but in non-renal model. Further elucidation of the mechanistic role of EGF via the EGFR pathway is warranted. Additionally, the adjunctive use of receptor tyrosine kinase inhibitors that have high safety profile in combination with maintenance immunosuppression might present a novel therapeutic approach for reducing allograft injury during AMR.
