Types of Graft Rejection

🐭 RAT series

Points to Ponder for NEET-PG, FMGE & NEXT

• Hyperacute rejection is the most severe and occurs rapidly due to pre-existing ABO incompatibility or anti-HLA antibodies.
• Acute cellular rejection involves T cell infiltration and can be reversible with treatment.
• Acute antibody-mediated rejection involves antibody attack on the graft endothelium and is characterized by C4d deposition.
• Chronic rejection is characterized by progressive fibrosis and loss of function in the graft.

Graft rejection is the immune system’s attack on a transplanted organ or tissue. The type of rejection can be classified based on the timing of onset and the mechanisms involved.

Hyperacute Rejection:

• Occurs within minutes to hours after transplantation.
• Most commonly caused by:
  • ABO blood group incompatibility: Pre-existing antibodies against A or B antigens on the donor organ.
  • Pre-formed anti-HLA antibodies: Recipient has antibodies against donor’s Human Leukocyte Antigen (HLA) molecules.
• Pathogenesis:
  • Antibodies activate the complement system.
  • Complement fragments deposit on blood vessel walls in the graft, leading to thrombosis (blood clot formation) and tissue damage.
• Clinical features: Rapid decline in graft function.
• Kidney involvement: Graft becomes cyanotic (bluish), mottled (discolored), and flaccid (limp).

Acute Rejection:

• Occurs within the first 6 months post-transplant.
• Two main types:
  • Acute Cellular Rejection (T cell-mediated):
    • Caused by T lymphocytes directly attacking the graft tissue.
    • Characterized by infiltration of the graft with mononuclear cells (lymphocytes and macrophages).
    • Usually reversible with prompt treatment.
    • May present as tubulitis: inflammation of the renal tubules, with involvement of both CD4+ and CD8+ T cells, and endothelial cells (lining of blood vessels).
  • Acute Antibody-mediated Rejection:
    • Caused by antibodies against the graft endothelium (lining of blood vessels).
    • Lesions involve inflammation of glomeruli (kidney filtering units) and peritubular capillaries (tiny blood vessels around tubules).
    • Characterized by deposition of C4d, a complement breakdown product, on the graft tissue.

Chronic Rejection:

• Most common type of graft rejection.
• Develops months to years after transplantation (usually after 6 months).
• Pathogenesis: Gradual fibrotic scarring of the graft due to various factors, including:
  • Chronic immune response.
  • Ischemia (reduced blood flow) to the graft.
  • Calcineurin inhibitor toxicity (medications used to suppress the immune system).
• Kidney involvement:
  • Glomerulopathy: Abnormalities of the glomeruli, including duplication of the basement membrane.
  • Peritubular capillaritis: Inflammation of small blood vessels around tubules, with thickening of their basement membranes.
  • Interstitial fibrosis and tubular atrophy: Progressive scarring and wasting away of the functional tissue in the kidney.

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