Distinct FOXP3 gene expression in the peripheral blood and inside renal allografts is associated with use of mTOR inhibitors and extended criteria kidney donor
Douglas Santos Costa1, Cinthia Dias1, Naiane do Nascimento Gonçalves1,2, Ida Maria Maximina Fernandes-Charpiot1,2, Maria Alice Sperto Ferreira Baptista1,2, Heloisa Cristina Caldas1,2, Mario Abbud-Filho1,2.
1Medicine , Laboratory of Immunology and Experimental Transplantation (LITEX), Medical School of Sao Jose do Rio, Sao Jose Do Rio Preto, Brazil; 2Kidney Transplant Unit, Hospital de Base, FAMERP/FUNFARME, Sao Jose Do Rio Preto, Brazil
Background: Trafficking of regulatory T cells (Tregs) modulate inflammatory response after kidney transplantation. There is scarce information on whether circulating and intragraft Tregs are similarly affected by immunosuppressive drugs (ISD) and by the type of deceased kidney donor.
Objectives: 1- to study the simultaneous gene and protein expression of the FOXP3 (forkhead-winged helix transcription factor) in the peripheral blood (PB) and within renal allografts; 2- to correlate FOXP3 expression with the immunosuppressive drugs (ISD) used and kidney donor type.
Methods: FOXP3 gene and protein expression were assessed by real-time PCR and immunohistochemical analysis in the peripheral blood (PB) and kidney biopsies (Bx) of patients receiving Tacrolimus (Tac; n=21) or Everolimus (Eve; n=19) at the 3rd month post-Tx. FOXP3 expression was correlated with donor type (standard – SCD or extended criteria – ECD donors), ISD, acute rejection (AR), delayed graft function (DGF), and serum creatinine (sCr) at one year.
Results: Eve-treated patients had a longer DGF duration (p=0.04) and a lower frequency of de novo post-Tx diabetes (p=0.03) compared with the Tac group. FOXP3 expression in the PB and Bx was greater in Eve than in Tac-treated patients. Immunohistochemistry did not show differences in the FOXP3 expression for both types of ISD. Recipients of SCD and ECD had similar gene and protein expression inside allografts and in the renal tissue regardless of the ISD. However, in the PB, ECD recipients treated with Eve (ECD/Eve) had higher FOXP3 expression than ECD/Tac (p=0.04) and SCD/Eve (p= 0.01). In the blood Eve and ECD kidney (OR= 5.6; p= 0.04 and OR= 8.7; p= 0,015, respectively) were independently associated with FOXP3 expression while in the Bx only Eve was associate with increased gene expression (OR=5.1; p= 0.03).
Conclusion: FOXP3 gene and protein expression does occur differently in the blood and inside allografts from recipients of ECD kidneys treated with mTOR inhibitors. We suggest caution when interpreting studies comparing outcomes based on the measurement of the FOXP3 gene expression in different tissues and compartments and kidney donor types.
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