Biomarker Candidate Discovery for Kidney Allograft Monitoring via Urinary Exosome Proteome Analysis

J. Kim¹, Y. Wee¹, M. Choi¹, H. Jung¹, J. Choi¹, H. Kwon¹, J. Jung¹, Y. Ko¹, D. Kim¹, K. Kim², Y. Cho³, H. Go³, Y. Kim¹, D. Han¹, S. Shin¹

¹Department of Surgery, Asan Medical Center, Seoul, Korea, Republic of, ²Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea, Republic of, ³Department of Pathology, Asan Medical Center, Seoul, Korea, Republic of

Meeting: 2019 American Transplant Congress

Abstract number: 359

Keywords: Graft failure, Kidney transplantation, Monitoring, Outcome

Session Information

Session Name: Concurrent Session: Biomarkers, Immune Monitoring and Outcomes III

Session Type: Concurrent Session

Date: Monday, June 3, 2019

Session Time: 4:30pm-6:00pm

Presentation Time: 4:42pm-4:54pm

Location: Room 306

*Purpose: There is a need for the development of noninvasive molecular biomarkers with high reliability and predictive power for early diagnosis and monitoring of any clinical condition after kidney transplantation. Nowadays, exosome can explain the mechanism of disease phenotype as well as progress.

*Methods: A total of 60 urine samples were collected at the time of check-up or 2 – 3 hours before the for-cause biopsy. In addition, living kidney donors were enrolled in this study and urine specimens were collected just before donor nephrectomy. They were classified into 5 groups, antibody-mediated rejection (ABMR) group (12 cases), T cell-mediated rejection (TCMR) group (8 cases), BK virus nephropathy (BKVN) group (5 cases), no major abnormality (NOMOA) group (11 cases) and donor (DONOR) group (24 cases). Exosome was fractionated from patient’s urine by stepwise ultra-centrifugation. Digested peptide mixture was desalted using C18 reverse phase chromatography and analyzed with high resolution mass spectrometry coupled with nano-flow liquid chromatography. And identification using sequence database analysis and label free quantitation (LFQ) analysis was performed using Proteome Discoverer to find biomarker candidates for kidney transplantation rejection monitoring.

*Results: Totally, 2,062 exosome proteins of 4,193 of urinary proteins were identified in the 5 groups. Among those proteins, 16 biomarker candidates were discovered to represent each pathologic status of kidney allograft. 8 biomarkers were selected for ABMR, 4 biomarkers represented TCMR and also 4 biomarkers were specific for BKVN. Label free quantitation results showed that there were several differential expressing proteins (DEPs) which can explain the pathway of each phenotype. Using DAVID bioinformatics database, we searched for characteristics of each biomarker. As results of gene ontology, innate immune response and complement activation pathway were activated in ABMR group. In TCMR group, proteins had not been well reported on DAVID bioinformatics database. In the BKVN group, translational initiation and protein binding biomarkers were shown to be increased.

*Conclusions: From urinary exosome proteome analysis, not only biomarker candidates for each type of rejection monitoring, but also candidate mechanism for rejection could be discovered. Further validation for biomarker candidates using large sample set from multi-center cohort will be done.

To cite this abstract in AMA style:

Kim J, Wee Y, Choi M, Jung H, Choi J, Kwon H, Jung J, Ko Y, Kim D, Kim K, Cho Y, Go H, Kim Y, Han D, Shin S. Biomarker Candidate Discovery for Kidney Allograft Monitoring via Urinary Exosome Proteome Analysis [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/biomarker-candidate-discovery-for-kidney-allograft-monitoring-via-urinary-exosome-proteome-analysis/. Accessed November 22, 2024.

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