title: Immune monitoring of immunosuppression withdrawal of liver transplant recipients.
abstract: Several studies have shown that some liver transplant recipients may tolerate immunosuppression withdrawal. Mechanisms and biomarkers of tolerance are not well known.
  
  
  METHODS
  Twenty-four LT patients with immunosuppression side-effects underwent progressive immunosuppression withdrawal. Peripheral lymphocyte populations and secretion of cytokines were analyzed at baseline and during withdrawal until tolerance (n = 15) or rejection (n = 9), as well as 3 months after tolerance achievement or rejection resolution (as follow-up). Immunological markers were compared among groups.
  
  
  RESULTS
  The percentages of CD3+CD4+ cells progressively decreased in both groups. CD3+CD8+ cells gradually increased in tolerant patients. B lymphocytes gradually decreased in tolerant and initially in non-tolerant patients, reverting at rejection. Regulatory T cells progressively increased until rejection in non-tolerants, decreasing to basal levels after renewing immunosuppression; no significant changes were found in tolerant patients. The percentages and absolute counts of natural killer cells significantly increased in both groups, being more evident in tolerant patients. The secretion of several cytokines was higher in non-tolerant patients when rejection was diagnosed.
  
  
  CONCLUSIONS
  The greater increase of natural killer cells in tolerant patients suggests their potential role in the tolerance phenomenon.
authors.affiliation: Liver Unit, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: García de la Garza
authors.affiliation: Division of Hepatology and Gene Therapy, Centro de Investigación Médica Aplicada, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Sarobe
authors.affiliation: Instituto de Investigación Sanitaria de Navarra (IdiSNA), Spain; Department of Immunology, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Juana
authors.initials: J
authors.lastname: Merino
authors.affiliation: Division of Hepatology and Gene Therapy, Centro de Investigación Médica Aplicada, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Lasarte
authors.affiliation: Liver Unit, Clínica Universidad de Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Spain; Centro de Investigación Biomédica en Red de enfermedades hepaticas y digestivas (CIBERehd), Spain.
authors.forename: Delia
authors.initials: D
authors.lastname: D'Avola
authors.affiliation: Division of Hepatology and Gene Therapy, Centro de Investigación Médica Aplicada, Pamplona, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Belsue
authors.affiliation: Department of Immunology, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Delgado
authors.affiliation: Division of Hepatology and Gene Therapy, Centro de Investigación Médica Aplicada, Pamplona, Spain.
authors.forename: Leyre
authors.initials: L
authors.lastname: Silva
authors.affiliation: Liver Unit, Clínica Universidad de Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Spain; Centro de Investigación Biomédica en Red de enfermedades hepaticas y digestivas (CIBERehd), Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Iñarrairaegui
authors.affiliation: Liver Unit, Clínica Universidad de Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Spain; Centro de Investigación Biomédica en Red de enfermedades hepaticas y digestivas (CIBERehd), Spain.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sangro
authors.affiliation: Department of Pathology, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Iosu
authors.initials: I
authors.lastname: Sola
authors.affiliation: Instituto de Investigación Sanitaria de Navarra (IdiSNA), Spain; Department of Surgery, Clínica Universidad de Navarra, Pamplona, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Pardo
authors.affiliation: Liver Unit, Clínica Universidad de Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Spain; Centro de Investigación Biomédica en Red de enfermedades hepaticas y digestivas (CIBERehd), Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Quiroga
authors.affiliation: Liver Unit, Clínica Universidad de Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Spain; Centro de Investigación Biomédica en Red de enfermedades hepaticas y digestivas (CIBERehd), Spain. Electronic address: iherrero@unav.es.
authors.forename: J
authors.initials: J
authors.lastname: Ignacio Herrero
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D005500:Follow-Up Studies; D006801:Humans; D007108:Immune Tolerance; D007159:Immunologic Tests; D016130:Immunophenotyping; D007165:Immunosuppression Therapy / Q000009:adverse effects; D016031:Liver Transplantation; D016131:Lymphocyte Subsets / Q000276:immunology*; D008991:Monitoring, Physiologic; D013375:Substance Withdrawal Syndrome / Q000175:diagnosis* / Q000209:etiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D028761:Withholding Treatment
chemical_list: D015703:Antigens, CD; D016207:Cytokines
keywords: Immunosuppression; Liver transplantation; Natural killer cells; Regulatory T cells; Tolerance