Graft Rejection Mechanisms: Hyperacute vs. Acute Rejection
Hyperacute rejection is antibody-mediated, but it is not reversible with steroids alone, making option (a) the only correct statement regarding graft rejection. 1, 2
Hyperacute Rejection
- Hyperacute rejection is definitively antibody-mediated, occurring within minutes to hours (0-7 days) after transplantation due to preformed donor-specific antibodies (DSAs) binding to donor HLA antigens on the endothelial cells of the graft 1, 2
- This process activates the complement cascade, resulting in rapid endothelial damage, microvascular thrombosis, and immediate graft failure 1
- Hyperacute rejection is characterized by the deposition of immunoglobulins and complement within the allograft microvasculature, leading to severe tissue injury 1
- Hyperacute rejection is NOT reversible with steroids alone, requiring more aggressive interventions such as plasmapheresis, IVIg, and potentially mechanical circulatory support in severe cases 1, 3
Acute Rejection
- Acute rejection is primarily T-cell mediated (not B-cell mediated), occurring days to months after transplantation 1, 4
- The diagnosis of acute cellular rejection is made by histological identification of interstitial leukocyte infiltration with various degrees of myocyte damage 1
- Acute cellular rejection responds to anti-cellular rejection therapies such as corticosteroids, with clinical improvement and resolution of histological rejection features 1
- Acute rejection does NOT occur over months but rather within days to weeks after transplantation, making it a more immediate concern than chronic rejection 4, 5
Antibody-Mediated Rejection (AMR)
- AMR can present as hyperacute, acute, or chronic rejection, depending on when the antibodies develop and when they cause injury 1
- Acute AMR requires clinical evidence of graft dysfunction, histological evidence of capillary injury, immunopathologic evidence of antibody-mediated injury, and serological evidence of anti-HLA or anti-donor antibodies 1
- Treatment of AMR typically involves multiple approaches including high-dose corticosteroids, plasmapheresis, IVIg, rituximab, and optimization of maintenance immunosuppression 3
- Chronic AMR is considered a major contributor to late graft loss and remains challenging to treat effectively 6
Treatment Considerations
- First-line treatment for acute rejection often includes high-dose corticosteroids, but antibody-mediated rejection (including hyperacute) requires additional therapies 3
- Maintenance immunosuppression with mycophenolate mofetil (MMF) has been shown to be effective in preventing acute rejection in transplant recipients 7
- For refractory cases of AMR, second-line therapies may include bortezomib, anti-complement antibodies, total lymphoid irradiation, or photopheresis 3
- Mechanical circulatory support such as ECMO may be considered as salvage therapy in cases of AMR with hemodynamic compromise 1
Clinical Implications
- Sensitive antibody detection methods are crucial before transplantation to prevent hyperacute rejection, especially in sensitized patients 2
- Flow cytometry or complement-dependent cytotoxicity assays should be used to detect preformed antibodies against donor tissues 4
- A positive crossmatch using sera with IgG antibodies to HLA antigens is a contraindication to transplantation 4
- Optimal matching of donor and recipient HLA antigens can reduce the incidence of acute rejection episodes and improve long-term graft survival 4