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Individualization in dosing regimens is the customization of medication doses for individual patients. Its necessity arises from the goal of maximizing therapeutic benefits while minimizing risks. This approach is pivotal because human responses to drugs can vary widely; what is effective for one person may be inadequate or excessive for another. Interpatient (intersubject) variability refers to differences in drug responses between individuals, while intrapatient (intrasubject) variability...
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Organ-specific differences in achieving tolerance.

Maria Lucia L Madariaga1, Daniel Kreisel, Joren C Madsen

  • 1aCenter for Transplantation Science, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts bDivision of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St Louis, Missouri cDivision of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA.

Current Opinion in Organ Transplantation
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PubMed
Summary
This summary is machine-generated.

Achieving organ transplant tolerance varies by organ type. Kidney transplant tolerance is feasible, but heart and lung transplants require distinct, more robust protocols for successful tolerance induction.

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Area of Science:

  • Transplantation immunology
  • Immunosuppression strategies
  • Organ-specific tolerance

Background:

  • Kidney allografts are considered 'tolerance-prone,' with established protocols for inducing tolerance.
  • Heart and lung allografts are 'tolerance-resistant,' posing significant challenges for tolerance induction.
  • Current tolerance induction protocols are not universally applicable across different organ types.

Purpose of the Study:

  • To investigate the differential responses of kidney, heart, and lung allografts to tolerance induction protocols.
  • To elucidate the mechanisms underlying organ-specific differences in allograft tolerance.
  • To identify strategies for overcoming challenges in achieving tolerance for 'tolerance-resistant' organs.

Main Methods:

  • Review of experimental and clinical data on allograft tolerance induction.
  • Analysis of factors contributing to differential tolerance outcomes.
  • Exploration of novel protocols, including mixed chimerism and cotransplantation of tolerogenic organs in nonhuman primates.

Main Results:

  • Successful allograft tolerance has been achieved in kidney transplantation, both experimentally and clinically.
  • Inducing tolerance in experimental heart and lung allografts remains challenging.
  • Emerging protocols in nonhuman primates show promise for mechanistic insights.

Conclusions:

  • Protocols successful for 'tolerance-prone' organs (kidneys, livers) are unlikely to work for 'tolerance-resistant' organs (hearts, lungs).
  • Separate, more robust clinical trials are necessary to achieve tolerance in heart and lung transplant recipients.
  • Understanding organ-specific mechanisms is crucial for developing effective tolerance strategies.