Treatment with mTOR inhibitors after liver transplantation enables a sustained increase in regulatory T-cells while preserving their suppressive capacity - 01/06/18
, Fabien Stenard a, 1, Géraldine Dahlqvist a, b, Clément Barjon a, Lynda Aoudjehane a, Olivier Scatton c, Filomena Conti a, dBienvenue sur EM-consulte, la référence des professionnels de santé.
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| pages | 8 |
| Iconographies | 3 |
| Vidéos | 0 |
| Autres | 0 |
Highlights |
• | Conversion to an mTOR inhibitor induced significant increase in blood Tregs. |
• | Tregs preserved their suppressive capacity after conversion. |
• | Conversion from Tac to mTOR inhibitor might be interesting in selected patients. |
Summary |
Background |
The mammalian targets of rapamycin (mTOR) inhibitors (sirolimus [SRL] and everolimus [EVR]) are used after transplantation for their immunosuppressive activity. Regulatory T-cells (Tregs) play a crucial role in immune tolerance. mTOR inhibitors appear to preserve Tregs, unlike Tacrolimus (Tac).
Aim |
The aim of this study was to evaluate the number and function of Tregs in liver transplant recipients before and after conversion from Tac to mTOR inhibitors.
Methods |
Fifteen patients with stable graft function where converted to SRL (n=5) or EVR (n=10). Tregs (CD4+ CD25+ FoxP3+ CD127low) number and activity were analysed prospectively in blood cells using flow cytometry, and functional assay.
Results |
Patients of both groups displayed a sustained rise in Treg levels after introduction of mTOR inhibitors (Treg levels at 3 months: 6.45±0.38% of CD4 T-cells, vs. baseline level of 3.61±0.37%, P<0.001; mean fold increase 2.04±0.73). In SRL group, 3-month Treg levels were 6.01±0.53 vs. 3.79±0.39; P=0.037, while in EVR group they were 6.63±0.67 vs. 3.54±0.51; P=0.001. By contrast, no statistical change was observed in an unconverted Tac control group. Tregs also preserved their functional ability to suppress activated T-cells.
Conclusion |
These results suggest that mTOR inhibitors induce a significant increase in Tregs while maintaining suppressive activity after LT.
Le texte complet de cet article est disponible en PDF.Keywords : mTOR inhibitor, Liver, Transplantation, Regulatory T-cells, Calcineurin inhibitor.
Abbreviations : CD, CNI, EVR, HCC, MMF, PBMC, PTLD, PSC, SRL, Tac, Tregs
Plan
Vol 42 - N° 3
P. 237-244 - juin 2018 Retour au numéro
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