title: A need for biomarkers of operational tolerance in liver and kidney transplantation.
abstract: Both kidney and particularly liver recipients can occasionally discontinue all immunosuppressive drugs without undergoing rejection. These patients, who maintain stable graft function off immunosuppressive drugs without clinically significant detrimental immune responses and/or immune deficits, are conventionally termed operationally tolerant and offer a unique paradigm of tolerance in humans. The immune characterization of operationally tolerant transplant recipients has recently received substantial attention. Operationally tolerant patients might exhibit a signature of tolerance that could potentially be useful to select recipients amenable to drug minimization or withdrawal. Furthermore, elucidation of the molecular pathways associated with the operational tolerance phenotype could provide novel targets for therapy. Particular emphasis has been placed on the use of blood samples and high-throughput transcriptional profiling techniques. In liver transplantation, natural killer related transcripts seem to be the most robust markers of operational tolerance, whereas enrichment in B cell-related gene expression markers has been consistently found in blood samples from operationally tolerant kidney recipients, suggesting that different mechanisms operate in the two situations. In this minireview, we summarize the main achievements of recently published reports focused on the identification of transcriptional markers of operational tolerance, we highlight their mechanistic and clinical implications and describe their methodological limitations.
authors.affiliation: Liver Transplant Unit, Hospital Clinic, IDIBAPS, CIBEREHD, Barcelona, Spain
authors.forename: M-C
authors.initials: MC
authors.lastname: Londoño
authors.forename: R
authors.initials: R
authors.lastname: Danger
authors.forename: M
authors.initials: M
authors.lastname: Giral
authors.forename: J-P
authors.initials: JP
authors.lastname: Soulillou
authors.forename: A
authors.initials: A
authors.lastname: Sánchez-Fueyo
authors.forename: S
authors.initials: S
authors.lastname: Brouard
mesh_terms: D000222:Adaptation, Physiological; D015415:Biomarkers; D006801:Humans; D016030:Kidney Transplantation; D016031:Liver Transplantation; D014158:Transcription, Genetic
chemical_list: D015415:Biomarkers