An age-independent gene signature for monitoring acute rejection in kidney transplantation

Brian I. Shaw, Daniel K. Cheng, Chaitanya R. Acharya, Robert B. Ettenger, Herbert Kim Lyerly, Qing Cheng*, Allan D. Kirk, Eileen T. Chambers*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Acute rejection (AR) remains a significant problem that negatively impacts long-term renal allograft survival. Numerous therapies are used to prevent AR that differ by center and recipient age. This variability confounds diagnostic methods. Methods: To develop an age-independent gene signature for AR effective across a broad array of immunosuppressive regimens, we compiled kidney transplant biopsy (n=1091) and peripheral blood (n=392) gene expression profiles from 12 independent public datasets. After removing genes differentially expressed in pediatric and adult patients, we compared gene expression profiles from biopsy and peripheral blood samples of patients with AR to those who were stable (STA), using Mann-Whitney U Tests with validation in independent testing datasets. We confirmed this signature in pediatric and adult patients (42 AR and 47 STA) from our institutional biorepository. Results: We identified a novel age-independent gene network that identified AR from both kidney and blood samples. We developed a 90-probe set signature targeting 76 genes that differentiated AR from STA and found an 8 gene subset (DIP2C, ENOSF1, FBXO21, KCTD6, PDXDC1, REXO2, HLA-E, and RAB31) that was associated with AR. Conclusion: We used publicly available datasets to create a gene signature of AR that identified AR irrespective of immunosuppression regimen or recipient age. This study highlights a novel model to screen and validate biomarkers across multiple treatment regimens.

Original languageEnglish
Pages (from-to)6977-6986
Number of pages10
Issue number15
StatePublished - 2020
Externally publishedYes


  • Acute rejection
  • Big data
  • Gene expression
  • Kidney transplant
  • Pediatrics


Dive into the research topics of 'An age-independent gene signature for monitoring acute rejection in kidney transplantation'. Together they form a unique fingerprint.

Cite this