Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6164821 | Kidney International | 2013 | 11 Pages |
Abstract
Current characterization of the immune risk in renal transplant patients is only focused on the assessment of preformed circulating alloantibodies; however, alloreactive memory T cells are key players in mediating allograft rejection. Immune monitoring of antidonor alloreactive memory/effector T cells using an IFN-γ Elispot has been shown to distinguish patients at risk for immune-mediated graft dysfunction, suggesting a potential tool for immunosuppression individualization. In this nonrandomized study, we prospectively assessed donor and nondonor T-cell alloreactivity in 60 highly alloreactive patients receiving calcineurin inhibitor-based immunosuppression and in non-T-cell alloreactive transplant recipients treated with a calcineurin inhibitor-free regimen. The impact was evaluated using 1-year allograft outcome. We found a strong association between ongoing antidonor T-cell alloreactivity and histological lesions of acute T cell-mediated rejection in 6-month protocol biopsies, distinguishing those patients with better 1-year graft function, regardless of immunosuppression regimen. Interestingly, evidence for enhanced immune regulation, driven by circulating Foxp3-demethylated regulatory T cells, was only observed among patients achieving antidonor T-cell hyporesponsiveness. Thus, prospective evaluation of donor-specific T-cell sensitization may add crucial information on the alloimmune state of transplanted patients to be used in daily clinical practice.
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Authors
Oriol Bestard, Josep M. Cruzado, Marc Lucia, Elena Crespo, Linda Casis, Birgit Sawitzki, Katrin Vogt, Carme Cantarell, Joan Torras, Edoardo Melilli, Richard Mast, Alberto Martinez-Castelao, Montse Gomà , Petra Reinke, Hans-Dieter Volk, Josep M. Grinyó,