Steroid free immunosuppression is associated with enhanced Th1 transcripts in kidney transplantation
2017
Abstract Background
Steroidavoidance in immunosuppression in kidney transplantation offers several
metabolic advantages, however it is associated with higher early acute
rejection rate. Cellular and molecular mechanisms of this phenomenon remain poorly understood. Methods In this single center observational study, low-risk kidney transplant recipients randomized into large multicenter prospective ADVANCE trial with
steroidavoidance/early withdrawal and center standard of care treated patients were monitored for 12 months. The expressions of 28 transcripts, associated with
alloimmuneresponse and operational tolerance, were evaluated in the peripheral blood using RT-qPCR at 0, 7, 14, 90 and 365 postoperative days (POD) and in the protocol graft biopsy at 3 months while lymphocyte subpopulations were analyzed by flow-cytometry within the follow-up. Results Both
steroidavoidance and withdrawal regimens were associated with significantly higher
granzyme B(
GZMB) transcript at POD 14 and
perforin1 ( PRF1 ) transcript at POD 7. The higher interleukin 2 ( IL-2) expression at POD 7 was detected only in the
steroidavoidance group. Initial
steroidsdecreased the expression SH2D1B transcript at POD14 and there were no further differences in other operational tolerance transcripts among groups. The statistically significant decrease in absolute numbers of peripheral NK cells in the first 14 days was observed in the standard of care group only. There were no differences in analyzed intrarenal transcripts in 3-month biopsies among groups. Conclusions The enhanced expression of some of Th1 associated transcripts and limited effects on NK cells of
steroidavoidance immunosuppression suggest higher susceptibility for early acute rejection.
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