Chronic Transplant Rejection

Summary

Chronic Rejection is a type of transplant rejection that happens months to years after receiving a new transplant. In chronic rejection, damage is mediated by both T-cells and antibodies directed against the graft. While immunosuppression can block acute (fast) rejection, subtle damage still occurs over time, eventually leading to chronic rejection.  Repeated injury and cytokine signalling over time leads to smooth muscle proliferation and development of scar tissue as interstitial fibrosis or arteriosclerosis. Ultimately, this results in luminal obliteration, a classic sign of chronic transplant rejection. 

Key Points

• Chronic Rejection
  • Occurs months to years after transplant (chronic)
  • Slow, accumulated damage caused by sensitization against donor antigens
    • Cellular (T-cell-mediated) and Humoral (B-cell-mediated) damage
      • Both a Type IV and Type II Hypersensitivity Reaction
  • Repeated damage and healing cycles lead to fibrosis/sclerosis (scarring)
    • Interstitial fibrosis
    • Arteriolosclerosis
  • Cytokine signalling from T cells leads to smooth muscle proliferation
  • Scar tissue and smooth muscle growth lead to luminal obliteration
    • Bronchiolitis obliterans (lung)
    • Accelerated atherosclerosis (heart)
    • Chronic graft nephropathy (kidney)
    • Vanishing bile duct syndrome (liver)