Early Detection of Kidney Graft Dysfunction by FoxP3 and CD25 Transcripts

Abstract

Background: Kidney transplantation (KTx) is the most effective treatment for end-stage renal disease. Early detection of at-risk patients, before the need for biopsy, through monitoring the transcript or protein levels of certain immune factors is crucial for improving clinical outcomes. Objectives: This cross-sectional study, conducted between 2019 and 2020 at Abu Ali Sina Hospital, aimed to evaluate the expression levels of three critical Treg markers, including forkhead box P3 (FOXP3), CD25, and interleukin-2 (IL-2), to assess the immune tolerance induced by Tregs for the early detection of kidney graft dysfunction. Methods: The study enrolled 39 kidney transplant recipients (KTRs) who were categorized as stable graft recipients (SGR; n = 21) or non-stable graft recipients (non-SGR; n = 18) without any viral infection. A healthy control group (n = 15) was included. Expression levels of FOXP3, CD25, and IL-2 were measured in peripheral blood mononuclear cells (PBMCs) collected during the first week post-transplantation using real-time PCR and analyzed via the Livak (2-ΔΔCt) method. The Mann-Whitney test assessed differences between SGR and non-SGR groups, while potential biases were minimized through careful participant selection, blinding during measurements, and consideration of measurement bias. Results: Expression levels of FOXP3, CD25, and IL-2 were higher in KTRs compared to controls. Specifically, CD25 expression was significantly higher in the non-SGR group compared to the SGR group (P = 0.001), while FOXP3 showed a non-significant increase (P = 0.475). The IL-2 expression level exhibited a non-significant decrease (P = 0.374) in the non-SGR group compared to the SGR group. Conclusions: Our findings indicate that increased FOXP3 and CD25 expression levels in PBMCs imply a larger Treg population and may aid in the early detection of at-risk kidney graft recipients prior to biopsy. However, the findings are limited by the small sample size of recipients and the reliance on flow cytometry for detecting the Treg population and associated markers.