Reduction of HLA donor specific antibodies in heart transplant patients treated with proteasome inhibitors for antibody mediated rejection.

Autor: Horn ET; University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania, USA., Xu Q; Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Dibridge JN; UPMC Presbyterian Hospital, Department of Pharmacy, Pittsburgh, Pennsylvania, USA., Huston JH; Department of Cardiology, UPMC Heart and Vascular Institute, Pittsburgh, Pennsylvania, USA., Hickey GW; Department of Cardiology, UPMC Heart and Vascular Institute, Pittsburgh, Pennsylvania, USA., Kaczorowski DJ; Department of Cardiothoracic Surgery, UPMC Heart and Vascular Institute, Pittsburgh, Pennsylvania, USA., Keebler ME; Department of Cardiology, UPMC Heart and Vascular Institute, Pittsburgh, Pennsylvania, USA., Zeevi A; Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Jazyk: angličtina
Zdroj: Clinical transplantation [Clin Transplant] 2023 Dec; Vol. 37 (12), pp. e15132. Date of Electronic Publication: 2023 Sep 13.
DOI: 10.1111/ctr.15132
Abstrakt: In this project, we describe proteasome inhibitor (PI) treatment of antibody-mediated rejection (AMR) in heart transplantation (HTX). From January 2018 to September 2021, 10 patients were treated with PI for AMR: carfilzomib (CFZ) n = 8; bortezomib (BTZ) n = 2. Patients received 1-3 cycles of PI. All patients had ≥1 strong donor-specific antibody (DSA) (mean fluorescence intensity [MFI] > 8000) in undiluted serum. Most DSAs (20/21) had HLA class II specificity. The MFI of strong DSAs had a median reduction of 56% (IQR = 13%-89%) in undiluted serum and 92% (IQR = 53%-95%) at 1:16 dilution. Seventeen DSAs in seven patients were reduced > 50% at 1:16 dilution after treatment. Four DSAs from three patients did not respond. DSA with MFI > 8000 at 1:16 dilution was less responsive to treatment. 60% (6/10) patients presented with graft dysfunction; 4/6 recovered ejection fraction > 40% after treatment. Pathologic AMR was resolved in 5/7 (71.4%) of patients within 1 year after treatment. 9/10 (90%) patients survived to 1 year after AMR diagnosis. Using PI in AMR resulted in significant DSA reduction with some resolution of graft dysfunction. Larger studies are needed to evaluate PI for AMR.
(© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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