Clinical and Prognostic Correlates of pAMR Grading in Patients with Suspect Antibody Mediated Rejection

Purpose Antibody mediated rejection (AMR) is a serious emerging issue in the management of heart transplant (HT) recipients. Although consensus criteria currently define pathological diagnosis of AMR (pAMR), the clinical drawbacks of the pAMR criteria in term of graft function and prognosis, as well as pAMR relationship with donor specific antibodies, (DSA) are unexplored. Methods and Materials In this study we analyze the correlation between pAMR grading, hemodynamic features, DSA detection, and subsequent prognosis in a cohort of consecutive HT recipients with suspected AMR. Results We included 184 patients, with estimated 7-year graft survival of 84±4%, after biopsy. Luminex assay was available in 86 patients, of whom 24 (28%) positive for DSA. pAMR was diagnosed in 72 (39%) recipients (61, pAMR1 and 11 pAMR2). Capillary wedge pressure was higher in patients with pAMR≥1 than in those with pAMR 0 (P=0.03) but we found no difference in hemodynamic data between pAMR 1 and 2. Patients with DSA had a lower cardiac output (P=0.02). However, DSA did not correlate with pAMR grading, but were more often detected in patients with mixed rejection (cellular and AMR), than in those with pAMR alone (P=0.03). Significant angiographic vasculopathy (CAV) accounted for 30% of total deaths, regardless of any rejection grade, and was associated with 12% yearly mortality. pAMR grading per se, on the other hand, was not associated with graft survival, while mixed rejection accounted for a 3.6 times increased risk of graft-related death, in patients without CAV (P=0.04). Conclusions While showing that pathological signs of AMR were associated with a worse hemodynamic profile, with however no differences between pAMR 1 and 2 grades, this study provide suggestive evidence that DSA co-activate both cellular and antibody-mediated graft injury, and that mixed rejection, not AMR alone, drives poor outcome. These data shed new light on the clinical significance of pAMR grading, and brings attention to the adverse consequences of mixed rejection, as opposed to “pure” AMR.