OR10 Genetic predisposition to interleukin-10 production influences epstein-barr virus reactivation after renal transplantation

Aim Epstein–Barr virus (EBV) is responsible for posttransplant lymphoproliferative disorder (PTLD) after solid organ transplantation. A poor anti-EBV immune response in transplant recipients ultimately leads to EBV reactivation and complications. Genetic predisposition of cytokine production is a feature of variation in cytokine gene regulatory regions that may influence the anti-EBV immune response. We analyzed a panel of 17 cytokine gene variants and examined their influence on EBV reactivation after kidney transplantation. Methods A total of 270 renal transplant recipients (discovery cohort, n  = 189 and validation cohort, n  = 81) were analyzed. Seventeen gene variants located in the regulatory and/or exonic regions of 11 cytokine/cytokine receptor genes were genotyped by Luminex based SSO panels or direct sequencing. EBV reactivation was defined by EBV DNAemia. Results Three variants of IL-10 promoter region (-1082G/A, −819C/T, −592C/A) that lead to low production of IL-10 cytokines were found strongly associated with EBV reactivations. The multivariate logistic regression analysis showed that recipients carrying low IL10 producing haplotypes (ATA) have higher incidence of EBV reactivation ( p  = 0.005, HR = 8.8, 95% CI: 2.4–21.2) (Fig. 1). The competing risk regression analysis showed that the cumulative incidences of EBV reactivation in recipients carrying low IL-10 producing (ATA) haplotype was 24% (95% CI: 18–52%), whereas those in recipients carrying high IL-10 producing (GCC) haplotype was only 3% (95% CI: 1–8%). Conclusions Renal transplant recipient carrying low IL-10 producing gene variants have higher incidence of EBV reactivation. The findings may lead to development of a better and broader predictive model for EBV reactivations after transplantation involving genetic, serum and functional biomarkers. Download full-size image