Construction and identification of a chronic antibody ⁃ mediated rejection model of renal graft in mice
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1Department of Urology,the Second Affiliated Hospital of Nanjing Medical University,Nanjing 210011 ; 2.Departmentof Urology,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029 ,China

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    Abstract:

    Objective:Construction and identification of a chronic antibody - mediated rejection(cABMR)model of renal graft in mice. Methods:Male 6-8 weeks old BALB/cH2d and C57BL/6H2b mice were randomly divided into the syngeneic control group,cell - mediated rejection group,acute antibody - mediated rejection(aABMR)group,cABMR group 1,cABMR group 2,cABMR group 3. Pathological staining and Banff score were performed to diagnose the transplanted kidneys,survival curves were plotted,the levels of complement fragment C3d deposition,peripheral blood IgG class donor-specific antibody(DSA),serum creatinine(Cr)and serum urea nitrogen(BUN)were detected in transplanted kidney tissues,the expression of CD3 + T cells,CD19 + B cells,F4/80 labelled macrophages,Ly6G labelled myeloid cells were detected. Results:cABMR group 1 met ABMR diagnostic criteria with 80% postoperative survival rate and negligible CD3+ T cell expression,thus selected for subsequent studies. Compared to the control group,the C3d - positive exoression regions were significantly increased in the cABMR group and the average fluorescence intensity of IgG DSA in peripheral blood was notably enhanced. Serum Cr and BUN levels in peripheral blood were significantly higher. Compared to aABMR,the cABMR model of transplanted kidneys showed more extensive peritubular capillary haemorrhage and dilatation,single nucleus infiltration in the glomeruli,and more typical tubular damage and brush border detachment in the tubules,higher Banff scores, significantly more positive areas of C3d expression,significantly higher mean fluorescence intensity of peripheral blood IgG DSA, significantly higher peripheral blood serum Cr and BUN levels. Incontrast to aABMR,cABMR group showed no siginificant infiltration of CD19+ B cells or CD3+ T cells in the renal interstitial or peritubular capillaries,but there was a more significant infiltration of renal interstitial F4/80 labelled macrophage and Ly6G labelled myeloid cell. Foxp3 and IL-10 expression were significantly reduced in the cABMR model,while the infiltration of IL-1β,IL-6,TNF-α and CCL2 inflammatory cytokines was significantly increased in cABMR model. Conclusion:A cABMR model with an extended survival period was successfully constructed and identified. This model can be used to assess the mechanisms and intervention strategies of cABMR,with high clinical application value.

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YU Qiqin, YANG Zexin, ZHANG Junqi, GUI Zeping, NI Bin, ZHENG Ming, SHEN Baixin, WANG Zijie, GU Min. Construction and identification of a chronic antibody ⁃ mediated rejection model of renal graft in mice[J].,2025,(8):1073-1081.

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  • Received:January 23,2025
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  • Online: August 13,2025
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