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Hot-topic debate on tolerance: immunosuppression withdrawal.

Alberto Sánchez-Fueyo1

  • 1Liver Transplant Unit, Hospital Clinic of Barcelona, University of Barcelona, August Pi i Sunyer Institute for Biomedical Research, Center for Biomedical Research in Hepatic and Digestive Diseases (CIBEREHD), Barcelona, Spain. afueyo@clinic.ub.es

Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
|August 19, 2011
PubMed
Summary

Liver transplants show natural acceptance due to inherent tolerogenic properties. Some patients achieve spontaneous operational tolerance (SOT), allowing safe withdrawal of immunosuppression, though its full prevalence is still under investigation.

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Area of Science:

  • Immunology
  • Transplantation Biology
  • Graft Acceptance

Background:

  • Liver allografts possess inherent tolerogenic properties, leading to spontaneous acceptance in many animal models.
  • Clinical liver transplantation requires less immunosuppression than other organs and shows resistance to rejection.
  • A subset of liver transplant recipients can discontinue immunosuppression, maintaining graft function without rejection, a state termed spontaneous operational tolerance (SOT).

Purpose of the Study:

  • To explore the phenomenon of spontaneous operational tolerance (SOT) in liver transplant recipients.
  • To investigate the prevalence and characteristics of SOT.
  • To identify potential biomarkers for SOT.

Main Methods:

  • Review of existing literature on liver allograft acceptance and immunosuppression.
  • Analysis of clinical outcomes in liver transplant recipients undergoing immunosuppression withdrawal.
  • Exploration of transcriptional patterns in tolerant vs. non-tolerant recipients.

Main Results:

  • Intentional immunosuppression withdrawal has led to successful weaning in approximately 20% of stable liver transplant recipients.
  • The true prevalence of SOT remains unknown but may be higher in specific pediatric and adult populations.
  • Rejection during weaning is typically mild and manageable without high-dose immunosuppression.
  • Tolerant recipients display distinct transcriptional profiles in blood and liver tissue.

Conclusions:

  • Liver allografts have intrinsic tolerogenic properties facilitating acceptance.
  • Spontaneous operational tolerance (SOT) is a viable state for some liver transplant recipients, allowing immunosuppression withdrawal.
  • Further research is needed to confirm the benefits of immunosuppression withdrawal on long-term morbidity and mortality.