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

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.

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Citation

Published Version (Please cite this version)

10.7150/thno.42110

Publication Info

Shaw, Brian I, Daniel K Cheng, Chaitanya R Acharya, Robert B Ettenger, Herbert Kim Lyerly, Qing Cheng, Allan D Kirk, Eileen T Chambers, et al. (2020). An age-independent gene signature for monitoring acute rejection in kidney transplantation. Theranostics, 10(15). pp. 6977–6986. 10.7150/thno.42110 Retrieved from https://hdl.handle.net/10161/21157.

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Scholars@Duke

Shaw

Brian Shaw

House Staff
Kirk

Allan Douglas Kirk

David C. Sabiston, Jr. Distinguished Professor of Surgery

I am a surgeon with interest in immune management of transplant recipients. I am particularly interested in therapies that influence T cell costimulation pathways and adjuvant therapies that facilitate costimulation blockade to prevent the rejection of transplanted organs without undue suppression of protective immunity. I am also interested in understanding how injury, such as that occurring during trauma or in elective surgery, influences immune responses and subsequent healing following injury.

Chambers

Eileen Tsai Chambers

Associate Professor of Pediatrics

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