Background: Acute antibody mediated rejection (AMR) is main barrier to long term renal graft survival. Mouse model is important to understand the mechenisms of AMR. However, current AMR model,sensitized by donor skin for 7 days, border clinical hyperacute rejection other than acue AMR, imposes limitations on studies that utilize this model. Our study aims to establish an improved AMR model to better simulate clinical process of acute renal graft AMR. Methods:6-8 weeks old male C3H and Balb/c mice were used as skin or kidney graft donors and recipients. Recipient animals were presensitized by transplanting skin grafts (ST) 7, 4, and 3 days before kidney transplantation (Tx) in the current ST-7dTx method versus our proposed ST-4dTx and ST-3dTx methods. Results:All the three groups met Banff criteria for AMR diagnosis:elevated donor specific antibody, histological features including glomerulitis, peritubular capillaritis, dilation of peritubular capillaries, tubular necrosis, hemorrhage, microthrombus, and C3d deposition. However, comparing with current model, our models have longer median survival time( 4 , 7, and 9 days in ST-7dTx, ST-4dTx, and ST-3dTx groups respectively), which allows more time for medical intervention. Our models didn't show prevalence of microthrombus in histology, which presented in current model. All recipient animals in ST-7dTx and ST-4dTx groups died within 14 days post Tx. 17% of recipients in ST-3dTx acquired long-term survival(>60d). Increased CD68+ macrophage cells and CD19+ B cells infiltration in presensitized recipient kidney grafts and spleens can be detected. Conclusions:Mice in our models are more in line with the clinical pathological characteristics of AMR. This allows for better study of AMR in the effort to establish better therapeutic methods. Especially in the ST-4dTx group that better mimicked clinical renal AMR.

CITATION INFORMATION: Zhao D, Li S, Liao T, Hua X, Han F, Luo Z, Liu X, Sun Q. Improved Mouse Renal Transplantation Model Simulating Clinical Antibody Mediated Rejection. Am J Transplant. 2017;17 (suppl 3).

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