Theranostics 2020; 10(15):6977-6986. doi:10.7150/thno.42110 This issue Cite

Research Paper

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

Brian I Shaw1, Daniel K. Cheng2, Chaitanya R. Acharya1, Robert B Ettenger3, Herbert Kim Lyerly1, Qing Cheng1✉, Allan D Kirk1,2, Eileen T Chambers1,2✉

1. Department of Surgery, Duke University Medical Center, Durham, United States
2. Department of Pediatrics, Duke University Medical Center, Durham, United States
3. Department of Pediatrics, UCLA Mattel Children's Hospital, Los Angeles, United States

Citation:
Shaw BI, Cheng DK, Acharya CR, Ettenger RB, Lyerly HK, Cheng Q, Kirk AD, Chambers ET. An age-independent gene signature for monitoring acute rejection in kidney transplantation. Theranostics 2020; 10(15):6977-6986. doi:10.7150/thno.42110. https://www.thno.org/v10p6977.htm
Other styles

File import instruction

Abstract

Graphic abstract

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.

Keywords: kidney transplant, acute rejection, gene expression, pediatrics, big data


Citation styles

APA
Shaw, B.I., Cheng, D.K., Acharya, C.R., Ettenger, R.B., Lyerly, H.K., Cheng, Q., Kirk, A.D., Chambers, E.T. (2020). An age-independent gene signature for monitoring acute rejection in kidney transplantation. Theranostics, 10(15), 6977-6986. https://doi.org/10.7150/thno.42110.

ACS
Shaw, B.I.; Cheng, D.K.; Acharya, C.R.; Ettenger, R.B.; Lyerly, H.K.; Cheng, Q.; Kirk, A.D.; Chambers, E.T. An age-independent gene signature for monitoring acute rejection in kidney transplantation. Theranostics 2020, 10 (15), 6977-6986. DOI: 10.7150/thno.42110.

NLM
Shaw BI, Cheng DK, Acharya CR, Ettenger RB, Lyerly HK, Cheng Q, Kirk AD, Chambers ET. An age-independent gene signature for monitoring acute rejection in kidney transplantation. Theranostics 2020; 10(15):6977-6986. doi:10.7150/thno.42110. https://www.thno.org/v10p6977.htm

CSE
Shaw BI, Cheng DK, Acharya CR, Ettenger RB, Lyerly HK, Cheng Q, Kirk AD, Chambers ET. 2020. An age-independent gene signature for monitoring acute rejection in kidney transplantation. Theranostics. 10(15):6977-6986.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image