ABMR

Antibody-mediated rejection (ABMR) is a form of organ transplant rejection driven by recipient antibodies directed against donor antigens, most commonly human leukocyte antigens (HLA). It can affect multiple solid organs, including kidney, heart, lung, and liver, and is a major cause of graft dysfunction and loss, particularly in sensitized recipients.

Pathophysiology of ABMR involves donor-specific antibodies (DSA) binding to donor endothelium, which activates the classical complement pathway. This leads to endothelial injury and microvascular inflammation, characterized in kidney transplants by glomerulitis and peritubular capillaritis, and often accompanied by deposition of C4d in peritubular capillaries. Chronic ABMR can lead to transplant glomerulopathy. Non-HLA antibodies may also contribute in some cases.

Diagnosis of ABMR typically relies on Banff criteria in kidney transplants, which require: (1) evidence of donor-specific antibodies or other evidence of antibody interaction with the graft, (2) histologic evidence of microvascular injury such as glomerulitis and/or capillaritis, and (3) C4d deposition or other supportive evidence of antibody-mediated injury. The criteria may be adapted for other organ transplants, emphasizing the combination of serology, histology, and evidence of antibody effect.

Management and prevention focus on reducing circulating antibodies, inhibiting antibody production, and suppressing the immune response. Treatments include plasmapheresis or plasma exchange, intravenous immunoglobulin, rituximab (anti-CD20), and, in select cases, proteasome inhibitors or complement inhibitors (e.g., eculizumab). Prevention strategies involve risk assessment and desensitization for sensitized patients, optimized immunosuppression, and careful donor-recipient matching. Outcomes vary with timing and severity of injury, but prompt recognition and treatment improve graft function and longevity.