*Purpose: As many as 30% of patients with chronic active antibody-mediated rejection (cAMR) lack HLA-specific antibodies. Recently, researchers identified clinical relevance of non-HLA antibodies, including anti-vimentin antibodies (AVA). Vimentin is an intermediate filament released by apoptotic cells and activated macrophages. AVA play a role in lung and heart transplant, but the role in kidney transplantation is not well established. We hypothesized AVA play a role in a rat model of cAMR via macrophage dependent mechanisms.

*Methods: Minor mismatch kidney transplantation was performed to generate a rat chronic rejection model. Four groups were assessed: syngeneic (Lewis donor to Lewis recipient), allogeneic (Fisher donor to Lewis recipient), sensitized (Fisher donor to Lewis recipient that received blood transfusion pre-transplant), and B cell deficient recipients (Fisher donor to B^-/- Lewis recipient). Animals were harvested at 6 months.

*Results: At 6 months, circulating AVA were increased in allogeneic compared to syngeneic recipients (168 ± 6 pg/uL vs 94 ± 10 pg/uL, p=0.0003). Vimentin deposition in the allograft was significantly higher in allogeneic (2.8 ± 0.4% vs 1.6 ± 0.2%, p=0.03) and sensitized recipients (3.5 ± 0.8% vs 1.6 ± 0.2%, p=0.008) compared to syngeneic recipients at 6 months. AVA correlated with IgG donor specific antibody levels (R²= 0.42, p=0.001) and CD68⁺ cells within the glomerulus (R²=0.50, p<0.0001). Allograft vimentin levels correlated with CD68⁺ cells within the renal allograft (R²=0.50, p=0.0001).

*Conclusions: We identified the presence of the non-HLA antibody, AVA, in a rat model of cAMR. Within the renal allograft, vimentin levels correlated with the extent of intragraft CD68⁺ macrophages. These findings suggest a macrophage dependent mechanism promotes vimentin exposure and generation of AVA in this model of cAMR. Intragraft vimentin and circulating AVA may be useful as biomarkers of disease activity in cAMR.

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