Graft Rejection: Types and Mechanisms

Hyperacute rejection is antibody-mediated, making option (a) the correct statement regarding graft rejection. 1, 2

Types of Graft Rejection

Hyperacute rejection is mediated by preformed donor-specific antibodies that are present in the recipient before transplantation 1
It occurs within minutes to hours (0-7 days) after transplantation when recipient antibodies bind to donor HLA antigens on the endothelial cells of the allograft 1
This type of rejection involves activation of the complement cascade, resulting in rapid tissue injury and graft failure 2
Hyperacute rejection is NOT reversed with steroids, making option (b) incorrect 3
Detection of preformed antibodies through flow cytometry or complement-dependent cytotoxicity assays is crucial to prevent hyperacute rejection 4

Acute rejection occurs days to months after transplantation 4
It is primarily T-cell mediated (not B-cell mediated), making option (c) incorrect 1
The diagnosis of acute cellular rejection is made by histological identification of interstitial leukocyte infiltration with myocyte damage 1
Acute rejection does not typically occur over months but rather within days to weeks after transplantation, making option (d) incorrect 4

AMR can be acute or chronic and is caused by donor-specific antibodies (DSA) 1
Required findings for acute AMR include 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 includes high-dose corticosteroids, plasmapheresis, IVIg, and rituximab 3

In hyperacute rejection, complement and immunoglobulin are deposited within the allograft microvasculature, leading to endothelial cell activation, cytokine upregulation, macrophage infiltration, increased vascular permeability, and microvascular thrombosis 1
Acute cellular rejection involves cytotoxic T-cell mediated damage to the allograft, characterized by interstitial leukocyte infiltration 1
Chronic antibody-mediated rejection is considered a major contributor to late graft loss 5

A positive crossmatch using sera with IgG antibodies to HLA antigens is a contraindication to transplantation due to the risk of hyperacute rejection 4
Patients with hyperacute rejection may require mechanical circulatory support as a salvage therapy 1
Maintenance immunosuppression with agents like mycophenolate mofetil (MMF) and sirolimus is important as they inhibit B-cell proliferation and immunoglobulin production 1, 6

Low-titer anti-HLA antibodies may not be detected by standard methods but can still cause hyperacute rejection 2
The absence of evidence of cellular rejection in a patient with graft dysfunction should prompt evaluation for antibody-mediated rejection 7
Optimal matching of donor and recipient HLA antigens can reduce the incidence of acute rejection episodes and improve long-term graft survival 4
While acute AMR can be treated with aggressive immunosuppression, chronic AMR has limited treatment options and carries a poor prognosis 8