Transplant Rejection

Description

Immune response to a graft’s genetically dissimilar antigens resulting in rejection of the transplanted organ:

• HLA incompatibility:
  • Most common cause of rejection
  • Rejection of solid organ transplants
• Blood group incompatibility:
  • Much less of a risk to graft survival than HLA incompatibility
  • May result in hyperacute rejection of primarily vascularized grafts (kidney and heart)
• 3 phases of rejection:
  • Hyperacute:
    • Immediate postoperative period
    • Antibody reaction to red cells or HLA antigens
    • Endothelial damage
    • Platelets accumulate, thrombi develop, and tissue necrosis occurs
    • Rare with careful donor–recipient matching
  • Acute:
    • Within the first 3 mo postop
    • At any time if immunosuppressant (IS) medication is stopped
    • T-cell–dependent process. Inflammatory cells infiltrate allograft, release cellular and humoral factors, destroys graft
    • Presents with constitutional symptoms and signs of transplant organ insufficiency
  • Chronic:
    • Occurs over years
    • Results in gradual organ failure

Epidemiology

Etiology

• Failure of immunosuppression:
  • Multiple medication interactions with cyclosporine, tacrolimus, or sirolimus including:
    • Phenobarbital, phenytoin, carbamazepine, rifampin, isoniazid
• Chronic rejection pathway:
  • Signal I: Alloantigen recognition
  • Signal II: Lymphocyte activation (costimulation)
  • Signal III: Clonal expansion
  • Becomes clinically apparent when rejection leads to graft inflammation and dysfunction
• Liver transplant rejection:
  • Acute: T-cell–mediated (cellular) rejection (TCMR)
  • 10–30% chronic: <5%
    • 1-wk–6-mo MC range to experience
• Cardiac transplant rejection:
  • Acute cellular rejection (ACR):
    • 13% of patients; within the 1st 3–6-mo chronic rejection
    • Accelerated atherosclerosis is the hallmark
    • Associated with change in IS therapy
• Lung transplant rejection:
  • ACR most common:
    • Risk 20–30% in the 1st year
  • Chronic rejection:
    • 25–40% of patients postop
    • MCC of death in 2nd postop year
    • Rejection caused by endothelial, vascular, and lymphocyte inflammation, recurrent acute rejection
• Bone marrow transplant rejection:
  • Acute graft vs host disease:
    • Immune attack of donor marrow on lung tissue
  • Chronic graft vs host disease:
    • 25–50% of patients
  • Marrow rejection:
    • MC in patients with plastic anemia who do not receive total body radiotherapy or in patients receiving mismatched or unrelated transplants