Investigating the role of miR-۱۰b, miR-۹۹a, and miR-۲۲۳ in acute kidney transplant rejection diagnosis

Current rejection diagnosis lacks reliable non-invasive tools, risking long-term kidney graft survival. To identify non-invasive biomarkers for timely acute rejection diagnosis in kidney transplant recipients. This investigation was designed to evaluate the diagnostic utility of specific circulating microRNAs (miRNAs) as novel indicators of kidney allograft rejection. Peripheral blood specimens were obtained from a cohort of ۱۵ patients with biopsy-confirmed acute T-cell-mediated rejection and ۱۰ age-matched healthy individuals. Peripheral blood mononuclear cells (PBMCs) were isolated via density gradient centrifugation, followed by total RNA extraction. Quantitative real-time polymerase chain reaction (qRT-PCR) assays were employed to measure the relative expression levels of miR-۲۲۳-۳p, miR-۹۹a-۵p, and miR-۱۰b-۵p. Statistical analyses of the qRT-PCR data identified significant dysregulation of all three miRNAs in the rejection cohort. Specifically, miR-۲۲۳-۳p and miR-۹۹a-۵p demonstrated marked elevation in expression compared to the control group (P < ۰.۰۰۱), with mean fold changes of +۰.۱۷۷ and +۰.۶۱۵, respectively. Conversely, miR-۱۰b-۵p exhibited significant suppression (P < ۰.۰۰۰۱), showing a mean reduction of ۰.۳۵۳-fold. Receiver operating characteristic (ROC) curve analysis indicated strong diagnostic performance for all candidates: miR-۲۲۳-۳p (AUC = ۰.۸۶), miR-۹۹a-۵p (AUC = ۰.۸۱), and miR-۱۰b-۵p (AUC = ۰.۹۱). The superior AUC value for miR-۱۰b-۵p suggests it possesses the highest discriminatory power. An unsupervised hierarchical clustering heatmap visually corroborated these expression patterns, depicting distinct upregulation (indicated in green) of miR-۲۲۳-۳p and miR-۹۹a-۵p and pronounced downregulation (indicated in red) of miR-۱۰b-۵p within the rejection group. While kidney transplantation is the definitive therapeutic intervention for ESRD, acute rejection continues to threaten graft viability. miR-۲۲۳-۳p, miR-۹۹a-۵p, and miR-۱۰b-۵p are promising blood biomarkers for early detection of transplant rejection.

کلیدواژه ها:

Acute T-cell-mediated Rejection ، Circulating microRNA Biomarkers ، Graft Rejection Immunologic Cascade ، MicroRNA ، Peripheral Blood Mononuclear Cells