Abstract 17210: Re-Defining Antibody Mediated Rejection With Donor-Specific Antibodies and Graft Dysfunction, on Behalf of the GRAfT Investigators

Abstract

Introduction: Heart transplant recipients with donor-specific antibodies (DSA) have increased risk for antibody-mediated rejection (AMR). However, many patients with graft dysfunction and DSA do not show AMR by endomyocardial biopsy (EMB). Hypothesis: We hypothesized that, similar to EMB-defined AMR, AMR defined as DSA presence + graft dysfunction on echocardiography is associated with 1) graft injury via elevated donor-derived cell-free DNA (dd-cfDNA) and 2) risk for long-term adverse outcomes. Methods: Adult heart transplant recipients from the Genomic Research Alliance for Transplantation (GRAfT, a prospective, multicenter study from 2015 to 2020) had DSA, echocardiogram, and dd-cfDNA evaluated at time of EMB. AMR was defined by EMB (pAMR ≥ 1), DSA/EF (DSA presence + LVEF drop by ≥ 10% to an LVEF ≤50%), or a composite of EMB or DSA/EF criteria. The composite long-term endpoint was death or long-term EF reduction ≤ 50% for >90 days. Results: 216 patients (29% Female, 39% Black race, mean age 52 ± 12 years) had 1489 EMB, 1959 DSA, 1821 echocardiogram, and 1190 dd-cfDNA evaluations. DSA were present in 71 patients (34%), predominantly class II (69%). AMR was detected by EMB in 16 subjects and by DSA/EF in 10 subjects. Median %dd-cfDNA for subjects with AMR by EMB was 0.63% (IQR 0.23-2.0), by DSA/EF was 0.40% (IQR 0.36-1.24), and for controls was 0.01% (IQR 0.001-0.10). There were 18 deaths and 10 subjects with long term EF reduction. As compared to controls, development of each AMR definition was associated with the composite long-term endpoint: AMR by EMB, HR=3.6, P =0.010; AMR by DSA/EF, HR=23.4, P <0.0001; composite AMR, HR=7.6, P <0.0001, Figure. Conclusions: Heart transplant recipients with EMB and EF/DSA AMR have similar evidence of graft injury via dd-cfDNA as well as risk of long-term adverse outcomes, as compared to those without AMR. Therefore, a composite definition of AMR, including EMB or DSA/EF may better allow for identification of patients at risk for graft failure.