Peripheral blood transcriptome analysis and development of classification model for diagnosing antibody‐mediated rejection vs accommodation in ABO‐incompatible kidney transplant. Issue 1 (26th August 2019)

• Record Type: Journal Article
• Authors: Jeon, Hee Jung; Lee, Jae‐Ghi; Kim, Kwangsoo; Jang, Joon Young; Han, Sung Won; Choi, Jinwoo; Ryu, Jung‐Hwa; Koo, Tai Yeon; Jeong, Jong Cheol; Lee, Jae Wook; Ishida, Hideki; Park, Jae Berm; Lee, Sang Ho; Ahn, Curie; Yang, Jaeseok
• Is Part Of: American journal of transplantation. Volume 20:Issue 1(2020)
• Page Start: 112
• Page End: 124
• Publication Date: 2019-08-26
• Subjects: ABO incompatibility -- accommodation -- basic (laboratory) research/science -- genetics -- kidney transplantation/nephrology -- kidney transplantation: living donor -- molecular biology: mRNA/mRNA expression -- rejection: antibody‐mediated (ABMR) -- translational research/science; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.15553
• Languages: English
• ISSNs: 1600-6135

Abstract

Abstract : The major obstacle to successful ABO blood group–incompatible kidney transplantation (ABOi KT) is antibody‐mediated rejection (AMR). This study aimed to investigate transcriptional profiles through RNA sequencing and develop a minimally invasive diagnostic tool for discrimination between accommodation and early acute AMR in ABOi KT. Twenty‐eight ABOi KT patients were selected: 18 with accommodation and 10 with acute AMR at the 10th day posttransplant protocol biopsy. Complete transcriptomes of their peripheral blood were analyzed by RNA sequencing. Candidate genes were selected by bioinformatics analysis, validated with quantitative polymerase chain reaction, and used to develop a classification model to diagnose accommodation. A total of 1385 genes were differentially expressed in accommodation compared with in AMR with P ‐adjusted < .05. Functional annotation and gene set enrichment analysis identified several immune‐related and immunometabolic pathways. A 5‐gene classification model including COX7A2L, CD69, CD14, CFD, and FOXJ3 was developed by logistic regression analysis. The model was further validated with an independent cohort and discriminated between accommodation and AMR with 92.7% sensitivity, 85.7% specificity, and 91.7% accuracy. Our study suggests that a classification model based on peripheral blood transcriptomics may allow minimally invasive diagnosis of acute AMR vs accommodation and subsequent patient‐tailored immunosuppression in ABOi KT. Abstract : This study proposes and validates a 5‐gene classification model based on peripheral blood transcriptomics for minimally invasive diagnosis of early acute antibody‐mediated rejection versus accommodation in ABO‐incompatible kidney transplant patients.