The impact of cytokine gene polymorphisms on Epstein-Barr virus infection outcome in pediatric liver transplant recipients

Background: Epstein-Barr virus (EBV) is associated with most cases of the post-transplant lymphoproliferative disorders developed during the first year after transplantation. The high EBV DNA load constitutes a major risk for the development of EBV-related lymphoproliferations. However, among transplant recipients there are patients with a chronically high viral load (CHVL) who do not develop lymphoproliferations. The polymorphism within cytokine genes might influence the susceptibility to, and contribute to the pathogenesis of the disease.

Objectives: The aim of this study was to analyze the genetic polymorphism in the selected cytokines with regard to EBV infection outcome in children after liver transplantation (LTx).

Study design: Thirteen cytokine/cytokine receptor polymorphisms were genotyped in 170 children after LTx, and related to: EBV DNAemia, CHVL onset and the length of CHVL carriage.

Results: The study revealed: the protective effect of rare homozygous and heterozygous IL-1β-511 and IL-1 receptor antagonist (IL-1RN VNTR) genotypes against viremia within the first year after LTx (OR=0.28, p=0.0007 and OR=0.35, p=0.009, respectively); the protective effect of CC chemokine ligand 2 (CCL2)+1543CT and TT genotypes against CHVL onset (OR=0.38, p=0.042); and the prolonged CHVL-resolution in IL12B 3'untranslated region (3'UTR) AC individuals (p=0.034).

Conclusions: This data suggests that carriage of IL-1β-511CT/TT and/or IL-1RN VNTR 1.2/2.2 genotype may be beneficial for combating EBV infection. This is the first study reporting the association of CCL2 and IL12B gene polymorphisms with the CHVL carriage in pediatric LTx recipients.