Pathologic basis of antibody-mediated organ transplant rejection

Abstract

A major progress has been made in understanding of ABMR of clinical transplants in the last 5 years. New pathology types of ABMR are not appropriately classified and updates to the Banff diagnostic criteria are required. Better diagnosis would help develop effective antiantibody treatment strategies and improve long-term outcomes for patients.

Update on pathology of antibody-mediated rejection in the lung allograft

“…Acute T-cellmediated rejection (ACR) is histologically characterized by varying degrees of perivascular lymphoid aggregates with or without accompanying acute lung injury [6]. The antibody-antigen interaction can cause graft injury by activation of complement and the complement cascade or through recruitment of leukocytes, such as natural killer cells, that may induce graft injury [9,10]. AMR is caused by interactions between preexisting or de-novo donor-specific antibodies (DSAs) and donor antigens, usually human leukocyte antigen (HLA) class I or II antigens on endothelial cells of capillaries in the donor organ.…”

A systematic review of the role of C4d in the diagnosis of acute antibody-mediated rejection

“…[26][27][28] In light of these developments, the role of each of the diagnostic criteria of AAMR, and in particular C4d, has been reconsidered in several recent important reviews. [29][30][31] To date, however, none have reviewed the literature systematically while considering the heterogeneity between studies in patient selection, conduct and the thresholds defining positive C4d, DSA assays or histopathological features of AAMR. To inform on the role of C4d in the evolving diagnostic schema of AAMR, we conducted a systematic review of the literature assessing the diagnostic performance of C4d compared with histopathological features of AAMR and DSA assays.…”

Review of Bortezomib Treatment of Antibody-Mediated Rejection in Renal Transplantation

“…ADCC occurs via binding the Fc region of the antibody to FccRIII (CD16) expressed by natural killer cells and macrophages, resulting in cell lysis (15). Endothelial-cell activation can also occur as a result of HLA binding by antibodies, resulting in the recruitment of leukocytes, platelet activation, and vascular thrombosis (31). Antibodies may also cross-link HLA I molecules, resulting in intracellular signaling cascades (80).…”