title: Markers of operational immune tolerance after pediatric liver transplantation in patients under immunosuppression.
abstract: A prospective identification of the estimated 20-50% of pediatric LTX recipients developing operational tolerance would be of great clinical advantage. So far markers of immune tolerance - T-cell subpopulations or gene expression profiles - have been investigated only retrospectively in successfully weaned patients. Fifty children aged 8-265 months (median 89) were investigated 1-180 months (median 44) after LTX under ongoing immunosuppression. T-cell subpopulations were measured during regular post-transplant visits using FACS (Vδ1- vs. Vδ2-γδ-T cells and Tregs). A Vδ1/Vδ2-γδ-T-cell ratio ≥1.42 previously reported in operational tolerance was found in 12 of 50 (24%) patients. In analogy, a Treg count ≥44 per μL was found in 35 of 50 (70%) patients and a Treg proportion ≥2.23% of CD3(+) -T cells in 39 of 50 (78%) patients. Only 9 of 50 patients (18%) fulfilled both criteria. The parameters Vδ1/Vδ2-γδ-T-cell ratio and Tregs were not significantly correlated to each other or with donor type or immunosuppression. Vδ1/Vδ2-γδ-T-cell ratio was more stable in serial examinations compared with Treg analyses. The observed proportion of 18% pediatric LTX patients with potential operational tolerance is in accordance with previous reports. However, clinical experience shows that rejections may happen even after long-time weaning of immunosuppression. This suggests that operational tolerance is a dynamic process, with uncertain prediction by Vδ1/Vδ2-γδ-T-cell ratio and/or Tregs under immunosuppression.
authors.affiliation: Department of General Pediatrics, University Hospital Schleswig-Holstein, Arnold-Heller-Strasse 3, Kiel, Germany. schulz-juergensen@pediatrics.uni-kiel.de
authors.forename: S
authors.initials: S
authors.lastname: Schulz-Juergensen
authors.forename: L
authors.initials: L
authors.lastname: Marischen
authors.forename: D
authors.initials: D
authors.lastname: Wesch
authors.forename: H H
authors.initials: HH
authors.lastname: Oberg
authors.forename: F
authors.initials: F
authors.lastname: Fändrich
authors.forename: D
authors.initials: D
authors.lastname: Kabelitz
authors.forename: M
authors.initials: M
authors.lastname: Burdelski
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D002469:Cell Separation; D002648:Child; D002675:Child, Preschool; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007165:Immunosuppression Therapy / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D017093:Liver Failure / Q000276:immunology / Q000628:therapy; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D012189:Retrospective Studies; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D017252:CD3 Complex; D007166:Immunosuppressive Agents; D016692:Receptors, Antigen, T-Cell, gamma-delta