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
Publication statusPublished - 2020 Jan 1

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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  • Cite this

    Jeon, H. J., Lee, J. G., Kim, K., Jang, J. Y., Han, S. W., Choi, J., Ryu, J. H., Koo, T. Y., Jeong, J. C., Lee, J. W., Ishida, H., Park, J. B., Lee, S. H., Ahn, C., & Yang, J. (2020). Peripheral blood transcriptome analysis and development of classification model for diagnosing antibody-mediated rejection vs accommodation in ABO-incompatible kidney transplant. American Journal of Transplantation, 20(1), 112-124. https://doi.org/10.1111/ajt.15553