Differential gene expression in non-adherent heart transplant survivors: Implications for regulatory T-cell expression.

Survival despite prolonged non-adherence with immunosuppression is rare but has been reported in kidney, lung, and liver transplantation. Its occurrence in heart transplantation is quite rare. Our study was prompted by an index patient who survived despite prolonged medication non-adherence. Prospective consent and blood collection were conducted for seven additional patients who presented in a similar fashion. The blood of patients who were diagnosed with rejection, stable early post-transplant, and stable more than 5 years post-transplant were all compared with a custom gene array focusing on T-regulatory cell processes. The two genes that were differentially expressed in every comparison were TGF beta and RNASEN with very low expression in the rejector group. The prolonged non-adherent group had the maximum expression for TGF beta but average RNASEN expression as compared to the low expression for rejectors and high for post-5 years patients. The patients presented survived for varying lengths of time without immunosuppression. The gene array analysis showed intriguing differences between these rare patients and important patient cohorts. Further efforts should be directed to finding and studying more patients who survive despite lack of prescribed immunosuppression. The mechanisms underlying this phenomenon may inform future advances in transplant immunosuppression.