Multi-Layered Immuno-Epigenetic Regulation of the YY1–SIRT7–H3K18Ac–PD-1/PD-L1 Axis in Renal Allograft Survival: Preliminary Findings
VOLUME
,
ISSUE
Correspondence
Published
Suggested Citation
DOI
License
Abstract
Objective:
This study aimed to characterize the immuno-epigenetic role of the YY1–SIRT7–H3K18Ac–PD-L1 axis in renal allograft survival and to identify molecular biomarkers associated with rejection.
Materials and Methods:
A total of 65 participants were enrolled: 20 patients with biopsy-confirmed allograft rejection, 25 with stable graft function, and 20 healthy controls. Blood samples were collected into EDTA-containing tubes and stored at −80°C. Total RNA was isolated and complementary DNA (cDNA) synthesized for gene expression analysis by real-time polymerase chain reaction (RT-PCR), using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and U6 small nuclear RNA (snRNA) as reference genes. Serum concentrations of SIRT7, H3K18Ac, and oxidative stress markers — superoxide dismutase (SOD) and glutathione (GSH) — were quantified by enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using SPSS v23.0 (p < 0.05).
Results:
Messenger RNA levels of STAT3, CD274 (PD-L1), H3F3A, SIRT7, and YY1 were significantly elevated in the rejection group, whereas PDCD1 (PD-1) was higher in the survival group (p<0.05). Long non-coding RNAs NEAT1, MALAT1, and GAS5 were upregulated in rejection (p<0.05). Significant alterations were detected in miR-21, miR-34a, miR-125, and miR-155 (p<0.01). SOD and GSH were decreased, while malondialdehyde (MDA) and catalase were elevated (p<0.05). NEAT1 and MALAT1 were predominantly upregulated in humoral rejection, whereas GAS5 was reduced.
Conclusion:
The YY1–SIRT7 epigenetic axis, in conjunction with PD-L1 signaling, appears to be implicated in immune evasion and inflammatory amplification following renal transplantation, supporting the potential utility of these molecules as immuno-epigenetic biomarkers of allograft rejection.
