Research Paper Volume 11, Issue 14 pp 5215—5231

Profiling of mRNA of interstitial fibrosis and tubular atrophy with subclinical inflammation in recipients after kidney transplantation

Qiang Fu 1, 2, 3, , Minxue Liao 1, 3, 4, , Cheng Feng 3, 5, , Jichao Tang 3, 5, , Rui Liao 3, 5, , Liang Wei 1, 3, , Hongji Yang 1, 3, 4, 5, , James F. Markmann 2, , Kai Chen 1, 3, , Shaoping Deng 1, 2, 3, 4, 5, ,

  • 1 Organ Transplantation Center, Sichuan Provincial People's Hospital and School of Medicine of University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China
  • 2 Transplant Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02148, USA
  • 3 Organ Transplantation Translational Medicine Key Laboratory of Sichuan Province, Chengdu 610072, Sichuan, China
  • 4 North Sichuan Medical College, Nanchong 637100, Sichuan, China
  • 5 Southwest Medical University, Luzhou 646000, Sichuan, China

received: June 11, 2019 ; accepted: July 16, 2019 ; published: July 25, 2019 ;

https://doi.org/10.18632/aging.102115
How to Cite

Copyright © 2019 Fu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Interstitial fibrosis and tubular atrophy (IFTA) with inflammation (IFTA-I) is strongly correlated with kidney allograft failure. Diagnosis of IFTA-I accurately and early is critical to prevent graft failure and improve graft survival. In the current study, through analyzing the renal allograft biopsy in patients with stable function after kidney transplantation (STA), IFTA and IFTA-I group with semi-supervised principal components methods, we found that CD2, IL7R, CCL5 based signature could not only distinguish STA and IFTA-I well, but predict IFTA-I with a high degree of accuracy with an area under the curve (AUC) of 0.91 (P = 0.00023). Additionally, IRF8 demonstrated significant differences among STA, IFTA and IFTA-I groups, suggesting that IRF8 had the capacity to discriminate the different classifications of graft biopsies well. Also, with Kaplan-Meier and log-rank methods, we found that IRF8 could serve as the prognostic marker for renal graft failure in those biopsies without rejection (AUC = 0.75) and the recipients expressing high had a higher risk for renal graft loss (P < 0.0001). This research may provide new targets for therapeutic prevention and intervention for post-transplantation IFTA with or with inflammation.

Abbreviations

AUC: Area under the curve; DEGs: Differentially expressed genes; IFTA-I: IFTA with inflammation; IFTA: Interstitial fibrosis and tubular atrophy; MCODE: Molecular Complex Detection; PPI: Protein-protein interaction; SPC: Semi-supervised principal components; STA: Stable function after kidney transplantation; TCMR: T cell-mediated rejection.