4.3 Article

Influence of everolimus-based treatment on circulating regulatory T cells after liver transplantation: Comparative study with tacrolimus-based therapy

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ELSEVIER MASSON, CORP OFF
DOI: 10.1016/j.clinre.2020.10.004

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Tolerance; Regulatory T cells; mTOR inhibitor; Calcineurin inhibitors; Liver transplantation

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  1. Rueil-Malmaison, France

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This study monitored Tregs levels and functionality in liver transplant patients under different immunosuppressive drugs, finding that everolimus may have a more positive impact on Tregs compared to tacrolimus. This provides a new approach for reducing the use of immunosuppressive drugs.
Liver transplantation remains the only treatment for terminal liver diseases. How-ever, immunosuppressive drugs required for allograft acceptance are toxic and may be responsible for severe side effects. Modulating the immune system to induce tolerance is a promising approach to reduce immunosuppressive regimen. More particularly, promoting nat-ural CD4(+) CD25(+) FoxP3(+) Tregs could be crucial in achieving tolerance. Contrary to calcineurin inhibitors, reports indicate that mTOR inhibitors may have a positive impact on Tregs. Here we present the first randomized prospective clinical study where Tregs levels from liver transplanted patients receiving either tacrolimus or everolimus were monitored for 6 months, starting from the day of transplantation. A total of 30 patients from four centers were monitored. Blood samples were obtained at day 0, day 14, one month, three months and six months post-transplantation. Flow-cytometry immunophenotyping of Tregs (CD4(+) CD25(+) CD127(-) FoxP3(+)) and functional assays with Tregs were performed to assess their immunosuppressive capacity. Levels of Tregs were significantly reduced after one month of standard tacrolimus-based immunosuppressive regimen (p < 0.05). Four months after conversion, levels of Tregs from patients treated with everolimus was significantly higher than patients under tacrolimus (p < 0.02). Functional assays demonstrated that Tregs conserved their capacity to suppress the proliferation of activated PBMC. (C) 2020 Published by Elsevier Masson SAS.

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