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

被引：38

作者：

Jung, Hee-Yeon ^{[1
]}

Lee, Chan-Hyeong ^{[2
]}

Choi, Ji-Young ^{[1
]}

Cho, Jang-Hee ^{[1
]}

Park, Sun-Hee ^{[1
]}

Kim, Yong -Lim ^{[1
]}

Moon, Pyong-Gon ^{[2
]}

Baek, Moon -Chang ^{[2
]}

Park, Jae Berm ^{[3
]}

Kim, Yeong Hoon ^{[4
]}

Chung, Byung Ha ^{[5
]}

Lee, Sang-Ho ^{[6
]}

Kim, Chan-Duck ^{[1
]}

机构：

[1] Kyungpook Natl Univ, Kyungpook Natl Univ Hosp, Sch Med, Dept Internal Med, Daegu, South Korea

[2] Kyungpook Natl Univ, Sch Med, Dept Mol Med, Daegu, South Korea

[3] Samsung Med Ctr, Dept Surg, Seoul, South Korea

[4] Inje Univ, Coll Med, Dept Internal Med, Busan, South Korea

[5] Catholic Univ Korea, Coll Med, St Marys Hosp, Dept Internal Med, Seoul, South Korea

[6] Kyung Hee Univ, Coll Med, Dept Internal Med, Seoul, South Korea

来源：

JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES | 2020年 / 1138卷

关键词：

Extracellular vesicle; Biomarkers; Proteomics; Chronic active antibody-mediated rejection; Kidney transplantation; IDENTIFICATION; EXOSOMES; RECEPTOR; PROLIFERATION; NEPHROPATHY; EXPRESSION; PROTEOMICS; SURVIVAL; IGA;

D O I：

10.1016/j.jchromb.2019.121958

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

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 multi center 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.

引用

页数：11

共 32 条

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