The Pathological Characteristics of Acute Antibody-Mediated Rejection in DA-to-Lewis Rat Orthotopic Liver Transplantation

Abstract

The category of acute antibody-mediated rejection (AMR) is not included in the Banff classification of liver transplantation pathology. We investigated the pathology of acute AMR using an orthotopic rat liver transplantation from DA-to-Lewis rats without immunosuppression. We studied liver graft samples at days 5, 7, and 9 to 11, focusing on the pathological characteristics of acute AMR. Progressive acute cellular rejection and AMR led to irreversible graft failure by day 11 ± 2. At day 5 immunoglobulin G (IgG) was deposited on endothelial cells in the portal veins and small arteries. Thereafter, at day 7 to day 11 the IgG deposition expanded on endothelial cells in portal veins and hepatic arteries, epithelial cells in bile ducts, sinusoids and hepatic cells in lobules. Light microscopic studies during the development of acute AMR showed interstitial edema in portal areas with neutrophilic infiltration. Rejecting grafts revealed congestion and/or thrombi in portal veins and hepatic arteries with neutrophil infiltration and fibrinogen deposition, severe degeneration of epithelial cells in bile ducts with periductal edema, intralobular edema, and hemorrhage with neutrophil infiltration and fibrinogen deposition, as well as hepatic cell degeneration and necrosis. In conclusion, acute AMR that developed in liver transplantation was characterized by endothelial cell injuries in microvasculature of portal veins, hepatic arteries, and sinusoids, accompanied by congestion, hemorrhage, thrombus formation, and neutophilic infiltration, as well as by bile duct and hepatic cell degeneration and necrosis.