Expression of Programmed Cell Death 1 and Helios Genes Correlates With rs872071A>G and rs12203592C>T Single-Nucleotide Polymorphisms of Interferon Regulatory Factor 4 in Patients with T-Cell-Mediated Rejection of Renal Allograft

Objectives: Acute T-cell-mediated rejection of the renal allograft is a serious posttransplant challenge that requires administration of high-dose immunosuppressive drugs with considerable side effects; therefore, specific targeting of T-cell responses may improve both prevention and treatment of T-cell-mediated rejection. A potential candidate for this purpose is interferon regulatory factor 4 because of its implication in differentiation and function of T cells. Our aim was to evaluate the frequency of the rs872071A>G and rs12203592C>T single-nucleotide polymorphisms of the interferon regulatory factor 4 gene and association of these 2 polymorphisms with the gene expression of programmed cell death 1 and Helios in patients with Tcell-mediated rejection versus stable recipients. Materials and Methods: Sixty recipients with T- cellmediated rejection and 60 age-matched and sexmatched stable recipients were recruited. Two single-nucleotide polymorphisms of interferon regulatory factor 4 gene, as well as the expression of programmed cell death 1 and Helios genes in peripheral blood mononuclear cells, were investigated with real-time polymerase chain reaction. Results: Programmed cell death 1 gene expression was reduced in patients with T-cell-mediated rejection versus stable recipients (P=.03). The frequency of rs872071A>G and rs12203592C>T single-nucleotide polymorphisms showed no significant difference between groups. Presence of the rs12203592C>T single-nucleotide polymorphism was directly correlated with the expression of programmed cell death 1 gene (P=.049), and rs872071A> G positivity was directly correlated with Helios gene expression (P=.008), which suggests an inhibitory role for interferon regulatory factor 4 on programmed cell death 1 and Helios molecules. Conclusions: Programmed cell death 1 gene expression was lower in patients with T-cell-mediated rejection versus stable recipients. Low-expressing singlenucleotide polymorphisms of interferon regulatory factor 4 could enhance the downstream gene expression of programmed cell death 1 and Helios immunoregulatory molecules. Therefore, specific inhibition of interferon regulatory factor 4 may promote tolerance induction in the allograft.