*Purpose: Antibody-mediated rejection (AMR) is a refractory rejection after donor-specific antibody (DSA)-positive or ABO blood-type incompatible liver transplantation (LT), due at least in part to lacking a standardized rodent model of AMR.

*Methods: Orthotopic LT was performed from male Dark Agouti rats (DA, 240-260g, donors) to male Lewis rats (LEW, 280-300g, recipients), served as non-sensitized controls (Group-NS). In pre-sensitized group (Group-PS), LEW were pre-sensitized by a preceding skin transplantat (2 x 2 cm²) from DA with subcutaneous aluminum adjuvant 4-6 weeks prior to LT.Tacrolimus was daily administered (0.1 mg/kg/day) after LT until sacrifice to suppress cellular rejections. Blood and liver tissues were sampled on post-transplant day (PTD)-1, -3, and -7 (n =5 each). Both IgG- and IgM-DSA titers in recipient sera were determined by flow cytometry.

*Results: AST, ALT, ALP, total bile-acid (TBA), and bilirubin were all significantly higher in Group-PS than in Group-NS (P<0.01). In particular, biliary damage markers, i.e. ALP, TBA, and bilirubin, were significantly deteriorated in Group-PS than in -NS on PTD-7 (P <0.001), followed by thrombocytopenia (P <0.05) and aggravated PT-INR (P <0.05). Histopathological grading (P <0.001) and C4d scores (P <0.001) were also significantly deteriorated in Group-PS than in -NS on PTD-7. As underlying mechanisms, we demonstrated significantly upregulated IgG- and IgM-DSA titers (P<0.001 and <0.05, respectively), accompanied with significantly-more infiltrated plasma cells to transplanted liver tissues (P <0.001) in Group-PS than in -NS on PTD-7.

*Conclusions: By a preceding skin sensitization with post-transplant tacrolimus, we developed a rat AMR model after LT that satisfies the Banff criteria for AMR diagnosis.

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