Development and validation of urinary exosomal microRNA biomarkers for the diagnosis of acute rejection in kidney transplant recipients

Frontiers in Immunology

Immunology

Yeong Hoon Kim¹  Jae Berm Park²  So-Young Lee³  Yu Ho Lee³  Hye Yun Jeong³  Ju-Young Moon⁴  Su Woong Jung⁴  Kyung-Hwan Jeong⁴  Hyeon Seok Hwang⁴  Jin Sug Kim⁴  Yang Gyun Kim⁴  Sang-Ho Lee⁵  Jung-Woo Seo⁵  Chan-Duck Kim⁶  Byung Ha Chung⁷  Dong Hyun Tae⁸  Junhee Seok⁸ 

[1] Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Republic of Korea;Department of Surgery, Samsung Medical Center, Seoul, Republic of Korea;Division of Nephrology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea;Division of Nephrology, Department of Internal Medicine, Kyung Hee University, Seoul, Republic of Korea;Division of Nephrology, Department of Internal Medicine, Kyung Hee University, Seoul, Republic of Korea;Research Laboratory, Medical Science Institute, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea;Division of Nephrology, Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea;Research Center, Division of Nephrology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea;School of Electrical Engineering, Korea University, Seoul, Republic of Korea;

关键词: kidney transplantation;    acute rejection;    urine;    exosome;    microRNA;   

DOI  :  10.3389/fimmu.2023.1190576

 received in 2023-03-21, accepted in 2023-04-27,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionAcute rejection (AR) continues to be a significant obstacle for short- and long-term graft survival in kidney transplant recipients. Herein, we aimed to examine urinary exosomal microRNAs with the objective of identifying novel biomarkers of AR.Materials and methodsCandidate microRNAs were selected using NanoString-based urinary exosomal microRNA profiling, meta-analysis of web-based, public microRNA database, and literature review. The expression levels of these selected microRNAs were measured in the urinary exosomes of 108 recipients of the discovery cohort using quantitative real-time polymerase chain reaction (qPCR). Based on the differential microRNA expressions, AR signatures were generated, and their diagnostic powers were determined by assessing the urinary exosomes of 260 recipients in an independent validation cohort.ResultsWe identified 29 urinary exosomal microRNAs as candidate biomarkers of AR, of which 7 microRNAs were differentially expressed in recipients with AR, as confirmed by qPCR analysis. A three-microRNA AR signature, composed of hsa-miR-21-5p, hsa-miR-31-5p, and hsa-miR-4532, could discriminate recipients with AR from those maintaining stable graft function (area under the curve [AUC] = 0.85). This signature exhibited a fair discriminative power in the identification of AR in the validation cohort (AUC = 0.77).ConclusionWe have successfully demonstrated that urinary exosomal microRNA signatures may form potential biomarkers for the diagnosis of AR in kidney transplantation recipients.

【 授权许可】

Unknown   
Copyright © 2023 Seo, Lee, Tae, Kim, Moon, Jung, Kim, Hwang, Jeong, Jeong, Lee, Chung, Kim, Park, Seok, Kim and Lee