Potential urinary extracellular vesicle protein biomarkers of chronic active antibody-mediated rejection in kidney transplant recipients.

Autor: Jung HY; Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea., Lee CH; Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea., Choi JY; Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea., Cho JH; Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea., Park SH; Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea., Kim YL; Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea., Moon PG; Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea., Baek MC; Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea., Berm Park J; Department of Surgery, Samsung Medical Center, Seoul, South Korea., Hoon Kim Y; Department of Internal Medicine, College of Medicine, Inje University, Busan, South Korea., Ha Chung B; Department of Internal Medicine, St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea., Lee SH; Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, South Korea., Kim CD; Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea. Electronic address: drcdkim@knu.ac.kr.
Jazyk: angličtina
Zdroj: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences [J Chromatogr B Analyt Technol Biomed Life Sci] 2020 Feb 01; Vol. 1138, pp. 121958. Date of Electronic Publication: 2019 Dec 26.
DOI: 10.1016/j.jchromb.2019.121958
Abstrakt: The aim of this study was to identify potential proteomic biomarkers for chronic active antibody-mediated rejection (CAMR) in kidney transplant recipients (KTRs). Among 385 KTRs enrolled in a cross-sectional multicenter study, 26 KTRs with biopsy-proven CAMR, 57 KTRs with long-term graft survival (LGS), and 10 rejection-free matched KTRs were included. A proteomic approach was employed to measure urinary extracellular vesicle (EV) changes in the KTRs. The urinary EVs were trypsin-digested using a gel-assisted protocol and quantified by label-free liquid chromatography with tandem mass spectrometry, using a data-dependent acquisition (DDA) mode. Western blot analysis was performed to confirm the protein levels for each candidate biomarker. Analysis of the isolated EV proteins revealed 93 and 97 proteins in the CAMR and LGS patients, respectively. Proteins that were identical in both groups were excluded and only high-significance proteins with a fold change of at least 1.5 were selected as candidate biomarkers. Six proteins (APOA1, TTR, PIGR, HPX, AZGP1, and CP) that were distinguishable between CAMR and LGS were selected. The proteins were confirmed by immunoblot analyses using independently acquired urinary EV samples. AZGP1 in particular was found to be a CAMR-specific proteomic biomarker that was distinguishable from the rejection-free control group with matching kidney function, duration of transplantation, and age. We identified and validated six proteomic biomarkers for CAMR and clarified one CAMR-specific proteomic biomarker in KTRs. Further clinical trials are needed before these rejection-specific biomarkers can be applied for the early prediction, diagnosis, and monitoring of the clinical response of KTRs to the treatment of CAMR.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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