Peripheral blood transcriptome analysis and development of classification model for diagnosing antibody-mediated rejection vs accommodation in ABO-incompatible kidney transplant

Hee Jung Jeon, Jae Ghi Lee, Kwangsoo Kim, Joon Young Jang, Sung Won Han, Jinwoo Choi, Jung Hwa Ryu, Tai Yeon Koo, Jong Cheol Jeong, Jae Wook Lee, Hideki Ishida, Jae Berm Park, Sang Ho Lee, Curie Ahn, Jaeseok Yang

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)112-124
Number of pages13
JournalAmerican Journal of Transplantation
Volume20
Issue number1
DOIs
StatePublished - 1 Jan 2020

Fingerprint

Gene Expression Profiling
Transplants
Kidney
Kidney Transplantation
Antibodies
RNA Sequence Analysis
Genes
Molecular Sequence Annotation
Computational Biology
Transcriptome
Immunosuppression
Logistic Models
Regression Analysis
Biopsy
Sensitivity and Specificity
Polymerase Chain Reaction

Keywords

  • 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

Cite this

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. / Peripheral blood transcriptome analysis and development of classification model for diagnosing antibody-mediated rejection vs accommodation in ABO-incompatible kidney transplant. In: American Journal of Transplantation. 2020 ; Vol. 20, No. 1. pp. 112-124.
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title = "Peripheral blood transcriptome analysis and development of classification model for diagnosing antibody-mediated rejection vs accommodation in ABO-incompatible kidney transplant",
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.",
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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. / 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.

In: American Journal of Transplantation, Vol. 20, No. 1, 01.01.2020, p. 112-124.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Peripheral blood transcriptome analysis and development of classification model for diagnosing antibody-mediated rejection vs accommodation in ABO-incompatible kidney transplant

AU - Jeon, Hee Jung

AU - Lee, Jae Ghi

AU - Kim, Kwangsoo

AU - Jang, Joon Young

AU - Han, Sung Won

AU - Choi, Jinwoo

AU - Ryu, Jung Hwa

AU - Koo, Tai Yeon

AU - Jeong, Jong Cheol

AU - Lee, Jae Wook

AU - Ishida, Hideki

AU - Park, Jae Berm

AU - Lee, Sang Ho

AU - Ahn, Curie

AU - Yang, Jaeseok

PY - 2020/1/1

Y1 - 2020/1/1

N2 - 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.

AB - 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.

KW - ABO incompatibility

KW - accommodation

KW - basic (laboratory) research/science

KW - genetics

KW - kidney transplantation/nephrology

KW - kidney transplantation: living donor

KW - molecular biology: mRNA/mRNA expression

KW - rejection: antibody-mediated (ABMR)

KW - translational research/science

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