Rejection of solid organ allografts is the result of a complex series of interactions involving coordination between both the innate and adaptive immune system with T cells central to this process.
Classification
Hyperacute rejection
Acute rejection
Chronic rejection
Annual incidences of early acute rejection, late acute rejection, and delayed graft function. Note that although rejection rates have fallen dramatically, rates of delayed graft function remain unchanged. The latter reflects nonimmunological variables such as ischemia times and use of suboptimal cadaveric donors. | Gjertson DW Impact of delayed graft function and acute rejection on kidney graft survival. Clin Transpl. 2000;467- 480
Hyperacute rejection: Within minutes
Occurs only in vascularized grafts
Mediator: Pre-existing recipient antibodies
MOA: Type II hypersensitivity
Complement activation & stimulation of endothelial cells to secrete Von Willebrand procoagulant factor → Platelet adhesion & aggregation → Intravascular thrombosis → Lesion → Graft loss
Findings: Intravascular thrombosis
Prophylaxis: Cross-match techniques between donor graft cells and recipient sera for:
ABO compatibility
Excluding presence of anti-donor human leukocyte antigen (HLA) antibodies
Acute rejection (< 15%): Within weeks
MOA:
T-cell dependent cellular rejection: Type IV hypersensitivity
B-cell dependent humoral rejection: Type II hypersensitivity
Findings: Vasculitis
Chronic rejection (M/C): After few months
MOA: Type II & IV hypersensitivity
Presence of tertiary lymphoid organs in graft (CHARACTERISTIC)
Findings (KAVITY):
Kidney injury
Accelerated arteriosclerosis
Vanishing bile duct syndrome
Interstitial fibrosis
T-cell mediated cytokine production
Bronchiolitis obliterans | yucky lung
Timeline of rejection event: Hyperacute, acute, and chronic rejection are classified by the type of injury exhibited. Each form is characterized by different immune activity. During Hyperacute Rejection (HR), normally occurring minutes to hours post-transplant, neutrophil recruitment and preexisting host antibodies activate the complement system of the immune system. During Acute Rejection (AR), normally occurring 6–90 days post-transplant, T cells have differentiated due to the activation of the cell-mediated immune response. Activated helper T cells signal B cells to produce antibodies against HLA of the graft. The T-cells cause the graft cells to lyse or produce cytokines that recruit other inflammatory cells, which may induce cytotoxicity and apoptosis, eventually causing necrosis of allograft tissue. In Chronic Rejection (CR), normally occurring after 90 days post-transplant, proliferation of smooth muscle cells and production of collagen by fibroblasts cause accelerated graft arteriosclerosis and results in fibrosis which can cause ischemia and cell death. Throughout these immune processes, there are biomarkers that can be found in three realms: the genome, the transcriptome, and the proteome. | Nasr, M., Sigdel, T., & Sarwal, M. (2016). Advances in diagnostics for transplant rejection. Expert review of molecular diagnostics, 16(10), 1121–1132. doi:10.1080/14737159.2016.1239530
