Effect of induction therapy on the expression of molecular markers associated with rejection and tolerance.

Eva Krepsova,Petra Hruba,Ondrej Viklicky,Birgit Sawitzki,Ilja Striz,Irena Tycova,Peter Wohlfahrt,Alena Sekerkova

doi:10.1186/s12882-015-0141-2

Abstract

BackgroundInduction therapy can improve kidney transplantation (KTx) outcomes, but little is known about the mechanisms underlying its effects.MethodsThe mRNA levels of T cell-related genes associated with tolerance or rejection (CD247, GZMB, PRF1, FOXP3, MAN1A1, TCAIM, and TLR5) and lymphocyte subpopulations were monitored prospectively in the peripheral blood of 60 kidney transplant recipients before and 7, 14, 21, 28, 60, 90 days, 6 months, and 12 months after KTx. Patients were treated with calcineurin inhibitor-based triple immunosuppression and induction with rabbit anti-thymocyte globulin (rATG, n = 24), basiliximab (n = 17), or without induction (no-induction, n = 19). A generalized linear mixed model with gamma distribution for repeated measures, adjusted for rejection, recipient/donor age and delayed graft function, was used for statistical analysis.ResultsrATG treatment caused an intense reduction in all T cell type population and natural killer (NK) cells within 7 days, then a slow increase and repopulation was observed. This was also noticed in the expression levels of CD247, FOXP3, GZMB, and PRF1. The basiliximab group exhibited higher CD247, GZMB, FOXP3 and TCAIM mRNA levels and regulatory T cell (Treg) counts than the no-induction group. The levels of MAN1A1 and TLR5 mRNA expressions were increased, whereas TCAIM decreased in the rATG group as compared with those in the no-induction group.ConclusionThe rATG induction therapy was associated with decreased T and NK cell-related transcript levels and with upregulation of two rejection-associated transcripts (MAN1A1 and TLR5) shortly after KTx. Basiliximab treatment was associated with increased absolute number of Treg cells, and increased level of FOXP3 and TCAIM expression.

Highlights

Induction therapy can improve kidney transplantation (KTx) outcomes, but little is known about the mechanisms underlying its effects
We showed that high ratios of CD4+Forkhead box P3 (FoxP3)+ Regulatory T cell (Treg) to effector T cells in peripheral blood of kidney graft recipients treated with basiliximab induction in early post-transplant period were associated with the absence of rejection [14]
T cellmediated rejection occurred within 12 months after Kidney transplantation (KTx) in 2/19 (10.5 %) of patients without induction and in 3/17 (17.6 %) of patients treated with basiliximab

Summary

Methods

The mRNA levels of T cell-related genes associated with tolerance or rejection (CD247, GZMB, PRF1, FOXP3, MAN1A1, TCAIM, and TLR5) and lymphocyte subpopulations were monitored prospectively in the peripheral blood of 60 kidney transplant recipients before and 7, 14, 21, 28, 60, 90 days, 6 months, and 12 months after KTx. Patients were treated with calcineurin inhibitor-based triple immunosuppression and induction with rabbit antithymocyte globulin (rATG, n = 24), basiliximab (n = 17), or without induction (no-induction, n = 19). Patients and samples Between September 2009 and November 2010, 75 consecutive recipients of kidney transplants from deceased donors were enrolled in a single-centre prospective study. Sixty patients met all of the following inclusion criteria for the study: 1) sufficient mRNA obtained during at least 7/9 sampling time-points, 2) unchanged maintenance immunosuppression, and 3) no steroid-resistant rejection.

Results

Discussion

Conclusion