The molecular refinement of the diagnosis of heart allograft rejection based on whole-transcriptome analyses faces several hurdles that greatly limit its widespread clinical application. The targeted Banff Human Organ Transplant gene panel (B-HOT, including 770 genes of interest) has been developed to facilitate reproducible and cost-effective gene expression analysis of solid organ allografts. We aimed to determine in silico the ability of this targeted panel to capture the antibody-mediated rejection (AMR) molecular profile using whole-transcriptome data from 137 heart allograft biopsies (71 biopsies reflecting the entire landscape of histologic AMR, 66 non-AMR control biopsies including cellular rejection and non-rejection cases). Differential gene expression, pathway and network analyses demonstrated that the B-HOT panel captured biologically and clinically relevant genes (IFNG-inducible, NK-cells, injury, monocytes-macrophage, B-cell-related genes), pathways (interleukin and interferon signaling, neutrophil degranulation, immunoregulatory interactions, endothelial activation) and networks reflecting the pathophysiological mechanisms underlying the AMR process previously identified in whole-transcriptome analysis. Our findings support the potential clinical use of the B-HOT-gene panel as a reliable proxy to whole-transcriptome analysis for the gene expression profiling of cardiac allograft rejection.

BACKGROUND: The addition of extracorporeal photochemotherapy (ECP) to standard immunosuppressive therapy has been suggested to be beneficial in the treatment of recurrent/persistent heart rejection.
METHODS: We reviewed medical data of heart transplant recipients who received ECP between 2010 and 2016 at our institution.
RESULTS: During the study period, eight patients underwent nine ECP courses. The median time from transplant to ECP was 18 months (range 9-54). Indications for ECP were recurrent rejection in 6 patients, persistent rejection in 1 patient and mixed rejection with hemodynamic compromise in 1 patient. Additional criteria for patients\' selection were represented by relevant comorbidities limiting the increase of immunosuppressive therapies. ECP was performed on an outpatient basis in 6 out of 8 patients. The median ECP duration was 12 months (range 1-18). Three out of 8 patients responded to ECP showing negative endomyocardial biopsies at the end of treatment. No additional rejection episodes were observed at their follow up (at 44, 72 and 31 months). Four of 8 patients failed to respond to ECP treatment, one patient has been judged not evaluable. Reduction of immunosuppressive therapies was obtained in all 3 responsive patients but also in 3 patients with a stable grade of rejection. The median duration of the follow up was 26 months (range 6-80). Two patients died at 6 and 21 months after beginning ECP. Survival after ECP was 78.2% at 26 months. No adverse effect or infectious complications associated with ECP were reported.
CONCLUSIONS: The low response rate (37.5%) in our case series could be partially explained by patient selection, the treated patients representing a high-risk sub-set group. Further studies to provide evidence of a role for ECP in heart rejection treatment or prophylaxis are needed.