Date: Saturday, May 30, 2020
Session Name: Biomarkers, Immune Assessment and Clinical Outcomes V
Session Time: 3:15pm-4:45pm
Presentation Time: 4:15pm-4:27pm
*Purpose: There is no non-invasive biomarker of alloimmune vascular injury. We have previously characterized exosome-like vesicles enriched in active proteasome and LG3 (ApoExo) that are released from apoptotic endothelial cells. Here, our aim was to evaluate whether ApoExo are increased in the circulation of kidney transplant recipients experiencing rejections involving the allograft vasculature.
*Methods: We performed a retrospective cohort study including consecutive kidney transplant recipients between 2008 and 2016 in 2 university affiliated centers and who underwent a kidney graft biopsy. Rejections were divided according to the presence of alloimmune vascular injury (grade 2A, 2B or 3 T-cell mediated rejection (TCMR) OR suspected/definite antibody-mediated rejection (AMR) according to the Banff 2017 classification) or the absence of alloimmune vascular injury (Banff borderline, grade 1A and 1B TCMR). We measured ApoExo in the recipient’s sera at the time of the biopsy using a technique enabling the detection of 20S proteasome activity at the single membrane vesicle level using high sensitivity flow cytometry and a permeable pan-reactive proteasome activity fluorescent probe.
*Results: Amongst the 248 study subjects, 34 had rejections involving the allograft vasculature (6 with pure grade 2/3 TCMR, 11 with mixed grade 2/3 TCMR and AMR, and 17 with AMR), 100 had tubulointerstitial TCMR, and 114 had normal surveillance biopsies. ApoExo were higher in patients with rejections involving the vasculature compared to those that did not (median 11, 57 x106 vesicles/ml in patients with vascular involvement versus 3, 74 x106 vesicles/ml with tubulointerstitial rejection only, p<0.001) and compared to patients with normal surveillance biopsies (median 3, 46 x106 vesicles/ml, p<0.001). On multivariate analysis adjusting for recipient age, sex and race, we observed an independent association between ApoExo and acute rejection with vascular involvement on the biopsy (odds ratio 1.07, 95% confidence interval 1.04-1.10 for each 106 increase in ApoExo). ApoExo were also correlated with estimated glomerular filtration rate at the time of biopsy (ρ=-0.20, p=0.001).
*Conclusions: ApoExo are strongly and independently associated with alloimmune vascular injury and functional impairment in kidney transplant recipients with acute rejection and represent a novel biomarker to assess the severity of vascular damage in the future.
To cite this abstract in AMA style:Dieude M, Boilard E, Allaeys I, Deneault-Marchand A, Turgeon J, Dore E, Lariviere-Beaudoin S, Karakeussian-Rimbaud A, Collette S, Senecal L, Hebert M, Cardinal H. Apoptotic Exosome-Like Vesicles are Associated with Alloimmune Vascular Injury in Kidney Transplant Recipients [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/apoptotic-exosome-like-vesicles-are-associated-with-alloimmune-vascular-injury-in-kidney-transplant-recipients/. Accessed February 27, 2021.
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