We propose anti-CD3-antibody-mediated contrast-enhanced ultrasonography using human T-lymphocytes for image-based diagnosis and differentiation of acute allograft rejection (AR) established in a rat renal transplantation model.
After tail vein injection of 30×106 human T-lymphocytes, microbubbles conjugated with a human anti-CD3 antibody were i.v. injected into male 10 weeks old uni-nephrectomized, allogeneically transplanted rats (Lewis-Brown Norway (LBN) to Lewis, aTX). Ultrasound was performed investigating the transplanted as well as the native kidney. In vivo results were confirmed with immunohistochemical stainings of CD3 after post mortem dissection. Syngeneically (sTX) transplanted rats (LBN to LBN), rats with ischemia/reperfusion injury (IRI, 45 min warm ischemia), and rats subjected to acute cyclosporine A toxicity (CSA) (50 mg/kg for 2 days i.p.) served as controls.
Accumulation of human T-lymphocytes was clearly detected by antibody-mediated ultrasonography und was significantly elevated on postoperative day 4 in allografts undergoing AR (5.41 ± 1.32 A.U., p < 0.05 vs. all controls, N = 4) compared to native control kidneys (1.09 ± 0.18 A.U.). No differences were found between native kidneys and sTX (0.99 ± 0.30 A.U.), CSA (0.12 ± 0.04 A.U.) and kidneys with IRI (0.46 ± 0.29 A.U.). The ultrasound signal intensity correlated well with results obtained by immunohistochemical analysis.
Antibody mediated contrast-enhanced ultrasonography detecting T-lymphocytes is an option to highly specific and non-invasively assess allograft rejection after rat renal transplantation. This method allows the discrimination of AR from acute tubular necrosis. Since it might easily be transferred into humans it is potentially clinically useful to improve the early diagnosis of AR, to investigate its kinetics and to monitor treatment efficiency.
To cite this abstract in AMA style:Grabner A, Kentrup D, Mühlmeister M, Pawelski H, Pavenstädt H, Schlatter E, Tiemann K, Reuter S. Non-Invasive Imaging of Acute Allograft Rejection by Ultrasound Detection of Microbubbles Targeted to T-Lymphocytes in a Rat Renal Transplantation Model [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/non-invasive-imaging-of-acute-allograft-rejection-by-ultrasound-detection-of-microbubbles-targeted-to-t-lymphocytes-in-a-rat-renal-transplantation-model/. Accessed December 6, 2023.
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