OR49 Effect of everolimus immunotherapy on HLA-antibody mediated activation of endothelial cells in heart transplantation

• Published in: Human immunology 2017-09, Vol.78, p.46-46
• Main Authors: Li, Fang, Rao, Ping, Hong, Longsheng, Fishbein, Michael C., Gjertson, David W., Reed, Elaine F.
• Format: Article
• Language: English
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2017.06.055

Donor-specific HLA antibodies (DSA) have been implicated in the process of acute and chronic antibody-mediated rejection (AMR) through their capacity to activate and injure the capillary endothelium of vascularized allografts. Ligation of HLA molecules on endothelial cells (EC) with HLA alloantibodies stimulates phosphorylation of S6 ribosomal protein (pS6RP) via the mechanistic target of rapamycin (mTOR). We hypothesize that expression of pS6RP in the capillary endothelium of allografts is a useful biomarker of rejection and can be used to assess the clinical efficacy of the mTOR inhibitor everolimus. 188 heart transplant patients from Novartis sponsored 2310 clinical multicenter trial were included in this study. Among them, 118 recipients were treated with reduced cyclosporine (CsA), everolimus (1.5 or 3.0mg/day) and steroids; 70 were treated with mycophenolate mofetil (MMF, 3g/day), standard CsA and steroids. AMR and acute cellular rejection (ACR) were diagnosed according to ISHLT criteria. Capillary endothelial staining of pS6RP was scored as 0–4 on endomycardial biopsies by immunohistochemistry. DSA was measured using single antigen luminex beads. 44.3% patients in MMF group and 37.6% patients in everolimus group developed DSA, predominantly against HLA class II (p=0.29, Fisher’s exact test). DSA producers demonstrated significantly higher pS6RP score (1.04±0.07 vs 0.73±0.05, p