Tolerance in liver transplantation: Biomarkers and clinical relevance.
Transplantation is the optimal treatment for end-stage organ failure, and modern immunosuppression has allowed important progress in short-term outcomes. However, immunosuppression poorly influences chronic rejection and elicits chronic toxicity in current clinical practice. Thus, a major goal in transplantation is to understand and induce tolerance. It is well established that human regulatory T cells expressing the transcription factor FoxP3 play important roles in the maintenance of immunological self-tolerance and immune homeostasis. The major regulatory T cell subsets and mechanisms of expansion that are critical for induction and long-term maintenance of graft tolerance and survival are being actively investigated. Likewise, other immune cells, such as dendritic cells, monocyte/macrophages or natural killer cells, have been described as part of the process known as "operational tolerance". However, translation of these results towards clinical practice needs solid tools to identify accurately and reliably patients who are going to be tolerant. In this way, a plethora of genetic and cellular biomarkers is raising and being validated worldwide in large multi-center clinical trials. Few of the studies performed so far have provided a detailed analysis of the impact of immunosuppression withdrawal on pre-existing complications derived from the long-term administration of immunosuppressive drugs and the side effects associated with them. The future of liver transplantation is aimed to develop new therapies which increase the actual low tolerant vs non-tolerant recipients ratio.
Alberto Baroja-Mazo, Beatriz Revilla-Nuin, Pacual Parrilla, Laura Martínez-Alarcon, Pablo Ramírez, José Antonio Pons, Biomedical Research Institute of Murcia (IMIB-Arrixaca-UMU), 30120 Murcia, Spain.
Alberto
A
Baroja-Mazo
Alberto Baroja-Mazo, Beatriz Revilla-Nuin, Pacual Parrilla, Laura Martínez-Alarcon, Pablo Ramírez, José Antonio Pons, Biomedical Research Institute of Murcia (IMIB-Arrixaca-UMU), 30120 Murcia, Spain.
Beatriz
B
Revilla-Nuin
Alberto Baroja-Mazo, Beatriz Revilla-Nuin, Pacual Parrilla, Laura Martínez-Alarcon, Pablo Ramírez, José Antonio Pons, Biomedical Research Institute of Murcia (IMIB-Arrixaca-UMU), 30120 Murcia, Spain.
Pascual
P
Parrilla
Alberto Baroja-Mazo, Beatriz Revilla-Nuin, Pacual Parrilla, Laura Martínez-Alarcon, Pablo Ramírez, José Antonio Pons, Biomedical Research Institute of Murcia (IMIB-Arrixaca-UMU), 30120 Murcia, Spain.
Laura
L
Martínez-Alarcón
Alberto Baroja-Mazo, Beatriz Revilla-Nuin, Pacual Parrilla, Laura Martínez-Alarcon, Pablo Ramírez, José Antonio Pons, Biomedical Research Institute of Murcia (IMIB-Arrixaca-UMU), 30120 Murcia, Spain.
Pablo
P
Ramírez
Alberto Baroja-Mazo, Beatriz Revilla-Nuin, Pacual Parrilla, Laura Martínez-Alarcon, Pablo Ramírez, José Antonio Pons, Biomedical Research Institute of Murcia (IMIB-Arrixaca-UMU), 30120 Murcia, Spain.
José Antonio
JA
Pons
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology; D006706:Homeostasis; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000166:cytology; D017093:Liver Failure / Q000276:immunology* / Q000601:surgery*; D016031:Liver Transplantation; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D020123:Sirolimus / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000166:cytology; D023001:Transplantation Tolerance
D015415:Biomarkers; D014408:Biomarkers, Tumor; D007166:Immunosuppressive Agents; D020123:Sirolimus
Biomarkers; Dendritic cells; Liver transplantation; Operational tolerance; Regulatory T cells
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