Background: Immunosuppression regimens effectively control acute rejection and decrease graft loss in the first year after transplantation; but long-term graft attrition rates remain stable beyond this point, due to a combination of drug toxicities and the emergence of chronic alloimmune responses. It is known that regulatory T cells (Tregs) play a role in limiting kidney transplant rejection and can potentially promote transplant tolerance. Despite this, there are a few prospective studies that prove the role of peripheral Tregs on long-term graft outcome.
The aim of our study was to analyze the influence of 1-year peripheral blood Tregs on long-term death censored graft survival.
Methods/Materials: Prospectively monitored peripheral blood Tregs by flow cytometry in Kidney Transplant Recipient (KTR) between 2005 and 2011. A total of 133 KTR were included in the study and followed up to 4 years after transplantation. Death censored graft survival was determined retrospectively in January-2017.
Results: Follow-up was 7.4 ± 2.9 years and 24.1% patients suffered death censored graft loss (DCGL). One-year peripheral Tregs were 17.4 ± 16.9 cells/mm3. Patients with high Tregs above the median value (14.57 cells/mm3) showed better death-censored graft survival (5-year 92.5% vs. 81.4%, Log-rank p = 0.030). One-year Tregs showed AUC-ROC of 63.1% (95%CI 52.9-73.2%, p = 0.026) for predicting DCGL. After multivariate Cox’s regression analysis, a high number of peripheral blood Tregs was a protective factor for DCGL (HR 0.961, 95%CI 0.924-0.998, p = 0.041) irrespectively of 1-year proteinuria and renal function.
Conclusion: A high number of peripheral blood Tregs at 1-year after kidney transplantation relates to a better long-term graft outcome. This relationship was independent of other significant 1-year variables. In this sense, peripheral blood Tregs can be useful as a biomarker to predict graft outcomes and to tailor immunosuppression.