Immunological Monitoring for the Detection of Allograft Rejection after Pediatric Liver Transplantation

Abstract

Introduction: Individualization of immunosuppressive medications is an important objective in transplantation medicine, but reliable biomarkers to identify tolerant patients among pediatric liver transplant recipients receiving immunosuppressive medications are still not established. We evaluate the potential of regulatory t cells, lymphocyte subsets and cytokine concentrations as potential biomarkers to individualize immunosuppressive medications. Methods: Lymphocyte subsets, regulatory T cells and serum cytokine concentrations were measured in 60 pediatric liver transplant recipients with acute and chronic rejection or normal graft function, and in 11 non-transplanted patients. We also compared these parameters in 12 pediatric living related liver transplant recipients and in 28 children following transplantation with a deceased donor organ presenting with good graft function. Results: Transplant recipients presenting with acute rejection had significantly lower numbers of CD4+ T-cells and increased CD8+ T-cell counts. Regulatory T cell numbers did not differ between children with rejection and patients with good graft function. Children with rejection showed increased concentrations of IL-2 and IFN-γ compared to asymptomatic patients, and high concentrations of IL-4 and TGF-β were detected in transplant recipients with good graft function. Transplant recipients who underwent living donor organ transplantation displayed significantly higher numbers of regulatory T-cell numbers and IL-4 serum concentrations compared to deceased donor organ recipients, both factors associated with beneficial outcome and transplantation tolerance. Conclusion: Cross-sectional parameters of peripheral regulatory T cells in pediatric liver transplant recipients do not seem to be valuable biomarkers for individualizing immunosuppressive therapy. Lymphocyte subpopulations, IL-2, IFN-γ, IL-4 and TGF-β serum concentrations may be potential marker for identification of rejection-prone children following liver transplantation. Living related liver transplantation may imply potentially beneficial immunological aspects.