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Identification of Antibodies Reactive to Vimentin in a Rat Kidney Transplant Model of Chronic Antibody-Mediated Rejection

S. Reese, N. Wilson, L. Ptak, J. Sullivan, W. Burlingham, A. Djamali, S. E. Panzer

University of Wisconsin Madison, Madison, WI

Meeting: 2019 American Transplant Congress

Abstract number: A37

Keywords: Antibodies, Kidney

Session Information

Session Name: Poster Session A: B-cell / Antibody /Autoimmunity

Session Type: Poster Session

Date: Saturday, June 1, 2019

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.

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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 May 9, 2025.

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