Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall C & D
*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.
To cite this abstract in AMA style:Reese S, Wilson N, Ptak L, Sullivan J, Burlingham W, Djamali A, Panzer SE. Identification of Antibodies Reactive to Vimentin in a Rat Kidney Transplant Model of Chronic Antibody-Mediated Rejection [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/identification-of-antibodies-reactive-to-vimentin-in-a-rat-kidney-transplant-model-of-chronic-antibody-mediated-rejection/. Accessed June 19, 2021.
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