#2894 pre-mRNA FOXP3 levels after transplant do not reflect risk of rejection

Nephrology Dialysis Transplantation(2024)

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Abstract Background and Aims Forkhead box P3 (FOXP3) is the master gene regulator of T regulatory cells, and is crucial for their suppressive function. In kidney transplant recipients, low post-transplant levels of FOXP3 in peripheral blood has been associated with increased risk of kidney allograft rejection. However, it is unknown if low post-transplant levels of FOXP3 pre-mRNA is also associated with increased risk of kidney allograft rejection. Here we aim to test if pre-mRNA FOXP3 levels are associated with the risk of rejection post-transplant in kidney transplant recipients. Method We collected blood samples from incident kidney transplant recipients the first day after transplantation. From these, we extracted peripheral blood mononuclear cell ribonucleic acid and measured pre-mRNA FOXP3 transcripts with quantitative reverse transcription polymerase chain reaction. Pre-mRNA FOXP3 levels were normalized to β-actin, and converted to a logarithmic scale. We collected data concerning rejection episodes through medical record review. Kidney transplant recipients that had at least one recorded acute kidney allograft rejection episode within the first three months post-transplant were defined as recipients with a rejection episode. Data is presented as median [interquartile range] and tested with Wilcoxon rank sum test. Results We measured pre-mRNA FOXP3 in 515 incident kidney transplant recipients, 52 experienced a rejection episode within the first three months post-transplant. Pre-mRNA levels did not differ between recipients with vs without rejection, logarithmic value of normalized pre-mRNA FOXP3 −4.48 [−4.63 to −4.10] vs −4.41 [−4.69 to −4.11], p = 0.80. The pattern persisted regardless of donor type, deceased recipients with rejection (N = 25) vs deceased recipients without—(N = 268), −4.47 [−4.62 to −4.26] vs −4.46 [−4.71 to −4.25], p = 0.90. Living ABO-compatible recipients with rejection (N = 19) vs living ABO-compatible recipients without—(N = 139), −4.49 [−4.64 to −4.14] vs −4.35 [−4.65 to −3.93], p = 0.30. Living ABO-incompatible recipients with rejection (N = 8) vs living ABO-compatible recipients without—(N = 56), −4.13 [−4.48 vs −3.88] vs −4.20 [−4.61 to −3.88], p = 0.70. Conclusion In kidney transplant recipients, early post-transplant abundance of pre-mRNA FOXP3 transcripts were similar regardless of risk of kidney allograft rejection post-transplant.
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