Comparing IRF-4 Gene Expression Between Acute T cell- Mediated Rejection and Stable Renal Transplant Recipients

Abstract

Introduction. Renal transplant rejection is one of the clinical challenges, which usually requires administration of immunosuppressive drugs causing serious side effects. Therefore, invention of effective and specific therapeutics is necessary to control undesired immune responses particularly T-cell reactions to allograft. Interferon Regulatory Factor-4 (IRF-4) due to its implication on T cells differentiation and function might be targeted to treat T cell-mediated cellular rejection (TCMR). The aim of this study was to investigate the association between IRF-4 gene expression and acute TCMR, as well as to examine the correlation between IRF-4 gene expression and cellular expression of Programmed cell death-1 (PD-1) and Helios molecules. Methods. Peripheral blood samples were obtained from 30 patients with biopsy proven acute TCMR and 30 stable recipients. IRF-4 gene expression was quantified using RT-PCR, and cellular expression of PD-1 and Helios were evaluated with flowcytometry. Results. IRF-4 gene expression was significantly increased in acute TCMR patients compared with stable recipients (P < .05). Helios protein expression was slightly decreased in TCMR group but this was not statistically significant. There was a negative correlation between IRF-4 gene expression and PD-1 as well as Helios frequency in the whole studied population. Conclusion. IRF-4 expression increases in acute TCMR which might also lead to a diminished expression of downstream immunoregulatory molecules such as PD-1 and Helios. Therefore, specific inhibition of IRF-4 may be helpful in managing acute TCMR.