title: Steroid free immunosuppression is associated with enhanced Th1 transcripts in kidney transplantation.
abstract: Steroid avoidance 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.
  
  
  
  In this single center observational study, low-risk kidney transplant recipients randomized into large multicenter prospective ADVANCE trial with steroid avoidance/early withdrawal and center standard of care treated patients were monitored for 12months. The expressions of 28 transcripts, associated with alloimmune response 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 3months while lymphocyte subpopulations were analyzed by flow-cytometry within the follow-up.
  
  
  
  Both steroid avoidance and withdrawal regimens were associated with significantly higher granzyme B (GZMB) transcript at POD 14 and perforin 1 (PRF1) transcript at POD 7. The higher interleukin 2 (IL-2) expression at POD 7 was detected only in the steroid avoidance group. Initial steroids decreased 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 14days was observed in the standard of care group only. There were no differences in analyzed intrarenal transcripts in 3-month biopsies among groups.
  
  
  
  The enhanced expression of some of Th1 associated transcripts and limited effects on NK cells of steroid avoidance immunosuppression suggest higher susceptibility for early acute rejection.
authors.affiliation: Transplant Laboratory, Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Hruba
authors.affiliation: Transplant Laboratory, Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Irena
authors.initials: I
authors.lastname: Tycova
authors.affiliation: Transplant Laboratory, Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Krepsova
authors.affiliation: Transplant Laboratory, Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Girmanova
authors.affiliation: Department of Clinical and Transplant Immunology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Alena
authors.initials: A
authors.lastname: Sekerkova
authors.affiliation: Department of Nephrology, Transplant Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Janka
authors.initials: J
authors.lastname: Slatinska
authors.affiliation: Department of Clinical and Transplant Immunology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Ilja
authors.initials: I
authors.lastname: Striz
authors.affiliation: Department of Clinical and Transplant Pathology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Honsova
authors.affiliation: Transplant Laboratory, Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; Department of Nephrology, Transplant Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. Electronic address: ondrej.viklicky@ikem.cz.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Viklicky
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D005786:Gene Expression Regulation; D007165:Immunosuppression Therapy / Q000379:methods; D016030:Kidney Transplantation; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D011446:Prospective Studies; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic
keywords: ADVANCE trial; Kidney transplantation; Rejection; Steroid elimination; Tolerance