Insights into Mixed Cellular and Antibody-Mediated Rejection (MR) in Pediatric Heart Transplant Recipients

“Mixed” rejection (MR) is currently defined as the presence of both cellular (CR) and antibody-mediated rejection (AMR) on endomyocardial biopsy (EMB). Whether MR is simply AMR and CR occurring simultaneously or a unique immunological entity is unclear based on limited experience in adults. In this study we sought to investigate some of the clinical characteristics of MR in the pediatric heart transplant (HTx) population. Pediatric patients (<19 yrs) who underwent HTx between 1985 and 2014 were identified in the UTAH Cardiac Transplant Program database. Patients were included in the study if they had at least one EMB. Only biopsies which included a score for both AMR and CR were included. MR was defined as the concomitant presence of CR (defined as any ISHLT score ≥ 1R) and AMR (defined as any pAMR value of ≥ 1). 135 patients with 1373 biopsies met inclusion criteria; 251 EMBs (18%) demonstrated MR. 44.4% of patients had no MR, 21.5% had 1 MR, 22.2% had between 2 and 5 MR, and 11.9% had more than 5 MR. The frequency of each of the 12 possible types of MR are detailed in the table below. “Mild” MR [1R/pAMR1(H+) and 1R/pAMR 1 (I+)] was the most common occurrence (123 out of 251, 50%). Higher grade CR was associated with higher grade AMR (pAMR 2 was most common with 2R, pAMR 3 with 3R), which was not the case with AMR. The incidence rate of MR in person/months is highest in the first month after transplant (0.27), followed by 0.15 at 2-3 months. After 3 months, the incidence rate of MR fell to less than 0.03. MR is highly prevalent (56%) amongst pediatric HTx recipients, occurring most commonly in the first 3 months after transplant. Our observations suggest that higher grade cellular rejection may induce a higher grade humoral response, whereas humoral rejection appears to proceed independently. Further investigation to better characterize and determine the clinical significance of MR is warranted in this patient population.Tabled 1Cellular rejection (ISHLT)1R2R3RpAMR 1(H+)77 8 1pAMR 1(I+)46 5 0pAMR 28119 0pAMR 3 4 010 Open table in a new tab