Elevated Myeloid: Plasmacytoid Dendritic Cell Ratio Associates With Late, but Not Early, Liver Rejection in Children Induced With Rabbit Anti-Human Thymocyte Globulin

Background. Dendritic cells (DC) play an important role in the induction and regulation of immune responses. Methods. Myeloid CD11c(+) DC (MDC), which may have inflammatory functions, and plasmacytoid CD123(+) DC (PDC), which may have tolerogenic potential, were measured by flow cytometric analysis, cross-sectionally, once, in 48 children, and longitudinally (pretransplant and at days 1-60, 61-200, and 201-400 posttransplant) in 30 children after liver transplantation (LTx). All children received cadaveric (n=53) or live donor (n=25) liver allografts with rabbit anti-human thymocyte globulin induction and steroid-free tacrolimus therapy. Rejectors in both groups were those children (n=35), who experienced biopsy-proven acute cellular rejection (ACR) within 60 days of DC monitoring. Results. Among rejectors in the longitudinal and cross-sectional cohorts, the MDC:PDC ratio was higher and was associated with decreased PDC frequencies. Logistic regression analysis, leave-one-out cross-validation, and receiver operating characteristic analysis applied to 30 cross-sectional subjects revealed that an MDC:PDC ratio more than or equal to 1.78 was associated with rejector status with sensitivity and specificity of 76.9% and 88.2%, respectively. Sensitivity and specificity were replicated in the 18 remaining cross-sectional subjects (88.8% and 78.8%, respectively), but not in longitudinally monitored subjects, during the early 60-day period after LTx (30.76% and 62.50%, respectively). A significant negative correlation was observed between tacrolimus whole blood concentrations and PDC frequencies (Spearman r= -0.370, P=0.005) in 48 cross-sectional subjects in whom DC subsets were monitored 1 to 3 years after LTx, but not during the early post-LTx period. Conclusions. We conclude that an elevated MDC:PDC ratio associates with liver graft rejection, which occurs after first year in children induced with rabbit anti-human thymocyte globulin.