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Recent advances in allograft vasculopathy.

Jonathan Merola1, Daniel D Jane-Wit, Jordan S Pober

  • 1aDepartment of Surgery bDepartment of Internal Medicine cDepartment of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.

Current Opinion in Organ Transplantation
|November 30, 2016
PubMed
Summary

Chronic rejection, specifically allograft vasculopathy, limits transplant longevity. Recent research reveals innate and adaptive immune responses drive this condition, with new therapies targeting these pathways now in clinical trials.

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Area of Science:

  • Transplantation immunology
  • Vascular biology
  • Immunopathology

Background:

  • Allograft vasculopathy is a primary cause of long-term organ transplant failure.
  • Understanding the immune mechanisms driving allograft vasculopathy is crucial for improving graft survival.

Purpose of the Study:

  • To review recent mechanistic insights into allograft vasculopathy pathogenesis.
  • To discuss current clinical evaluations of novel therapeutic strategies for chronic rejection.

Main Methods:

  • Review of preclinical studies on allograft vasculopathy mechanisms.
  • Analysis of recent clinical trial data for new therapeutic agents.

Main Results:

  • Adaptive immunity is a key driver, but natural killer cells also play a role in mediating vasculopathic changes.
  • Donor-specific antibodies (DSA) directly induce vascular inflammation and enhance endothelial alloimmunogenicity.
  • New clinical studies are evaluating mTOR and proteasome inhibitors.

Conclusions:

  • Allograft vasculopathy arises from complex innate and adaptive alloimmune responses.
  • Preclinical findings have identified promising therapeutic targets currently under investigation in clinical trials.