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Operational tolerance in intestinal transplantation.

Alexander Kroemer1, Khalid Khan1, Stuart S Kaufman1

  • 1Center for Translational Transplant Medicine, MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Georgetown University Medical Center, Washington, District of Columbia, USA.

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
|July 29, 2020
PubMed
Summary

This case report details the first instance of true operational tolerance in intestinal transplantation, where a patient successfully stopped all immunosuppression. This breakthrough demonstrates the potential for eliminating immunosuppression in intestinal transplant recipients.

Keywords:
T cell biologycellular biologyclinical research/practiceimmune regulationimmunosuppression/immune modulationintestinal (allograft) function/dysfunctionintestine/multivisceral transplantationmucosal immunitytolerancetranslational research/science

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Area of Science:

  • Transplantation immunology
  • Gastroenterology
  • Clinical case study

Background:

  • Intestinal transplantation outcomes are often limited by the need for long-term immunosuppression.
  • Operational tolerance has been achieved in other solid organ transplants, but not fully realized in intestinal transplantation.
  • Minimizing immunosuppression is crucial to reduce complications and improve long-term graft survival.

Observation:

  • A patient received a deceased-donor small intestinal and colon allograft and initially required standard immunosuppression.
  • Following an episode of graft-versus-host disease, the patient achieved excellent graft function.
  • Four years post-transplant, the patient voluntarily discontinued all immunosuppressive therapy against medical advice.

Findings:

  • The patient maintained normal graft function, full enteral autonomy, and showed no signs of rejection (histological or endoscopic) for 2-3 years after stopping immunosuppression.
  • Mechanistic studies revealed immune competence against third-party antigens and in vitro donor-specific hyporesponsiveness.
  • Donor-specific hyporesponsiveness was observed without evidence of donor macrochimerism.

Implications:

  • This case provides the first proof of principle for true operational tolerance in intestinal transplantation.
  • It supports the development of novel diagnostic and therapeutic strategies, such as cellular therapies, to eliminate immunosuppression.
  • This finding could potentially revitalize the field of intestinal transplantation by improving patient outcomes and reducing treatment burdens.