Background. In pediatric renal transplant recipients, persistent EBV viremia is associated with post-transplant lymphoproliferative disease (PTLD), but immune correlates of persistent viremia remain poorly defined. In this study the relationship between circulating lymphocyte subsets and persistent EBV viremia was examined in pediatric renal transplant patients.
Methods. Serial prospectively collected peripheral blood mononuclear cell samples from pediatric renal transplant patients were analyzed for CD4+ T cell subsets including Th1, Th2, Th17, CD4+ and CD8+ effector memory cells, and NK cells by flow cytometry for surface markers and intracellular cytokine staining. Patient demographics and EBV PCR results were extracted from patient records.
Results. 36 samples were obtained from 11 renal transplant patients over six months. Six patients had negative EBV PCR results at all time points. Five patients were EBV PCR positive, one of which was transient, while four remained positive with average PCR viral load of 10,507 copies/ml [range 515-34,710]. The two groups were similar with respect to EBV recipient status, age at transplant, and change in eGFR during the study. Patients with EBV viremia had significantly higher absolute CD4 T cell counts compared to patients without EBV viremia (mean +/- SD, 1629 + /-162 vs 903 + /-82, p = 0.0002). Within CD4 T cells subsets, patients with EBV viremia had a significantly lower percentage of CD4 + CCR4+ Th2 cells compared to those without EBV viremia (mean +/- SD, 3.80 + /-0.80 vs 7.14 + /-0.82, p = 0.019) as well as a significantly lower percentage of IL-4 producing CD4+ cells (0.67 + /-0.075 vs 2.26 + /-0.55, p = 0.002). No difference was seen in CD4+ or CD8+ effector memory, Th1, Th17 or NK cells.
Conclusion. In this cohort, persistent EBV viremia was associated with a statistically greater number of circulating CD4+ T cells, but statistically fewer circulating CD4+ Th2 cells and a blunted IL-4+ response compared to that found in patients without viremia. These results suggest that impairment of Th2 responses may contribute to persistent EBV viremia in pediatric renal transplant recipients.
Disclosures. All authors: No reported disclosures.