Donor-derived Cell-free DNA & Donor Specific Antibodies in Pediatric Heart Transplant Recipients

Background : Previous work in adult heart transplant (HTx) has shown donor-derived cell free DNA (dd-cfDNA) levels are elevated in the presence of endomyocardial biopsy (EMB) proven rejection as well as in the presence of donor specific antibodies (DSA). Less is known about impact of DSAs on dd-cfDNA levels in pediatric HTx patients. This study evaluates the relationship of dd-cfDNA with EMB results and DSAs at our center. Methods : Primary outcome of this retrospective analysis was a composite endpoint for allograft injury or risk for allograft injury (composite group), defined as the presence of either biopsy-proven acute cellular rejection (ACR) and/or DSAs. Secondary outcomes were the individual components of the composite outcome, including: 1) presence of ACR and 2) DSAs individually, as defined above. Results : Analysis consisted of 154 dd-cfDNA samples. Sixty dd-cfDNA levels were collected in the composite group, defined as the presence of ACR and/or DSAs. Of the samples in the composite group, 49 were paired with a positive DSA result, 6 had biopsy-proven ACR without positive DSAs and 5 had both biopsy-proven rejection and DSAs. dd-cfDNA was significantly higher in the composite group when compared to samples without evidence of graft injury (0.43% vs 0.09; p<0.001). Median dd-cfDNA levels were significantly higher in the positive EMB group when compared to the no rejection samples (1.10% vs 0.17%, p=0.003). Dd-cfDNA levels were significantly higher in the DSA positive group when compared to the DSA negative group (0.36% vs 0.08%, p <0.001). Conclusions : We demonstrate that in our cohort of pediatric HTx patients, dd-cfDNA levels are elevated in EMB proven ACR and in individuals with positive DSAs.