Transplant rejection
| Feature | Hyperacute Rejection | Acute Rejection | Chronic Rejection | Graft-vs-Host Disease (GVHD) |
|---|---|---|---|---|
| Onset | Mins-Hrs | Wks-Months (typ <3mo-1yr) | Months-Yrs | Variable (Acute <100d, Chronic >100d) |
| Patho/Etiology | Pre-formed Ab (Type II HSR); Thrombosis | Cell-mediated (T-cell vs donor MHC; Type IV HSR) &/or humoral | Chronic inflammation, fibrosis, atrophy; Complex | Donor T-cells attack recipient tissues |
| Presentation | Immediate graft failure, mottling, cyanosis | Graft dysfunction (e.g., ↑Cr, ↑LFTs), fever, tenderness | Gradual loss of fxn; Organ-specific sx | Acute: Rash, GI (diarrhea), Liver (jaundice). Chronic: Skin (sclerosis, lichenoid), sicca, multi-organ |
| Diagnosis | Clinical (intra-op); Bx: thrombosis/necrosis | Bx: Cellular infiltrate, endothelialitis | Bx: Fibrosis, arteriosclerosis (e.g., VOD, BOS) | Clinical; Bx of affected organ (skin, GI) |
| Mgmt/Tx | Irreversible; Graft removal | Immunosuppression (steroids, anti-lymphocyte Ab) | Poorly responsive; Optimize IS; Re-transplant | Immunosuppression (steroids); Supportive |
| Key Assoc. | ABO/HLA incompatibility; Prior sensitization | Most common type | Major cause of late graft loss | Allogeneic HSCT; Donor cells attack host |
| Buzzword | Pre-formed antibodies | T-cell mediated against graft | Fibrosis, insidious loss of function | Donor lymphocytes attack recipient |
Pathophysiology
Hyperacute rejection
- Humoral rejection (type II hypersensitivity reaction): recipient's preformed cytotoxic antibodies against donor's class I HLA molecules or blood group antigens �?activation of the complement system and adhesion to cells �?thrombosis of vessels �?graft ischemia and necrosis
- Preformed antibodies against HLA antigens result from exposure to foreign HLA haplotypes during pregnancy, transfusion, or a previously rejected transplant.
Acute rejection
- Allorecognition �?T lymphocyte induced cell-mediated and/or humoral immunity
- Acute cellular rejection (type IV hypersensitivity reaction)
- Donor MHC class II antigens react with recipient CD4+ T cells, which then differentiate into Th1 helper T cells �?cytokine (INF-γ) release �?macrophage recruitment �?parenchymal and endothelial inflammation
- Donor MHC class I antigens react with recipient CD8+ T cells �?direct cytotoxic cell damage
- Acute humoral rejection (type II hypersensitivity reaction): recipient antibodies, formed before or after transplantation, react against donor HLA antigens
Chronic rejection
- Combination of humoral rejection (type II hypersensitivity reaction) and cellular rejection (type IV hypersensitivity reaction)
- Donor MHC class II antigens react with recipient CD4+ T cells �?differentiation into Th1 helper T cells �?cytokine (INF-γ) release �?macrophage recruitment �?parenchymal and endothelial inflammation
Graft-versus-host disease
Etiology
- Graft-versus-host disease (GvHD) is common in transplantation of lymphocyte-rich organs, including:
- Allogeneic hematopoietic stem cell transplantation
- Transfusion of nonirradiated blood products
- HLA mismatch (especially HLA-A, HLA-B, and HLA-DR) is associated with an increased risk of GvHD.