Transplant Rejection

Basics

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

Incidence And Prevalence Estimates

  • Solid organ transplants:
    • Over 45,000 organs transplanted yearly
    • Most common transplanted organs: Kidney, liver, heart, lung
    • Most common ED diagnosis: Infection
    • Up to 75% require hospitalization, but in-hospital mortality is low

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

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