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Peripheral blood transcriptome analysis and development of classification model for diagnosing antibody‐mediated rejection vs accommodation in ABO ‐incompatible kidney transplant
Author(s) -
Jeon Hee Jung,
Lee JaeGhi,
Kim Kwangsoo,
Jang Joon Young,
Han Sung Won,
Choi Jinwoo,
Ryu JungHwa,
Koo Tai Yeon,
Jeong Jong Cheol,
Lee Jae Wook,
Ishida Hideki,
Park Jae Berm,
Lee Sang Ho,
Ahn Curie,
Yang Jaeseok
Publication year - 2020
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.15553
Subject(s) - medicine , immunosuppression , kidney transplantation , abo blood group system , transcriptome , transplantation , immunology , gene , gene expression , biology , genetics
The major obstacle to successful ABO blood group–incompatible kidney transplantation ( ABO i 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 ABO i KT . Twenty‐eight ABO i 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 COX 7A2L , CD 69 , CD 14 , CFD , and FOXJ 3 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 ABO i KT .