Pediatric heart transplantation outcomes have improved over the last two decades, but this improvement is mostly isolated to the first three months after transplantation. Unfortunately, acute graft rejection remains a leading cause of graft loss and death. Pediatric recipients who require treatment for rejection have lower survival and a higher incidence of early development (within 3 years of transplant) of cardiac allograft vasculopathy. Importantly, the diagnosis of rejection is dependent on endomyocardial biopsy, an invasive procedure with inherent risks.

The central hypothesis of this proposal is that circulating miRNAs will be a viable biomarker for the detection of acute graft rejection in pediatric heart transplant recipients. Secondarily we hypothesize that circulating miRNAs will distinguish cellular vs antibody-mediated rejection. To address our hypotheses, we will perform miRNA arrays on banked serum samples obtained at the time of endomyocardial biopsy from CTOTC study subjects.

Specific Aim 1: Determine the profile of circulating miRNAs in pediatric heart transplant recipients with and without acute graft rejection. miRNA arrays will be performed on banked serum from identified subjects. The diagnosis of rejection will be based on endomyocardial biopsy results, and all serum will have been drawn on the same day the biopsy was obtained. We hypothesize that pediatric heart recipients with evidence of acute graft rejection on biopsy will have a distinct miRNA profile compared to those that are free from rejection.

Specific Aim 2: Define the miRNA profile in patients with acute cellular rejection (ACR) and antibody-mediated rejection (AMR). We hypothesize that the miRNA profile in those with ACR will differ from those with AMR.