A Peripheral Blood Gene Expression Signature to Diagnose Subclinical Acute Rejection
| Autor: | Huimin Shang, Zeguo Sun, Milagros Samaniego, Chengguo Wei, Lorenzo Gallon, Khadija Banu, Madhav C. Menon, Ciara N. Magee, Zhengzi Yi, Dirk Kuypers, Stephen I. Alexander, Arjang Djamali, Maarten Naesens, Evelyne Lerut, Jenny Xiang, Nader Najafian, Rex Neal Smith, Ivy A. Rosales, Karen L. Keung, Paolo Cravedi, Christopher Woytovich, Weijia Zhang, Weiqing Huang, Robert B. Colvin, Barbara Murphy, Samira S. Farouk, Philip J. O'Connell, Caixia Xi |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncology Adult Graft Rejection Male medicine.medical_specialty Microarray Biopsy Inflammation Kaplan-Meier Estimate 030230 surgery 03 medical and health sciences 0302 clinical medicine Risk Factors Clinical Research Internal medicine Gene expression Medicine Humans Prospective Studies Subclinical infection Whole blood Aged Oligonucleotide Array Sequence Analysis medicine.diagnostic_test business.industry Sequence Analysis RNA Gene Expression Profiling Graft Survival General Medicine Genomics Gene signature Middle Aged Kidney Transplantation 030104 developmental biology Nephrology Cohort Kidney Failure Chronic Female medicine.symptom business Biomarkers Immunosuppressive Agents |
| Zdroj: | J Am Soc Nephrol |
| ISSN: | 1533-3450 |
| Popis: | Background In kidney transplant recipients, surveillance biopsies can reveal, despite stable graft function, histologic features of acute rejection and borderline changes that are associated with undesirable graft outcomes. Noninvasive biomarkers of subclinical acute rejection are needed to avoid the risks and costs associated with repeated biopsies. Methods We examined subclinical histologic and functional changes in kidney transplant recipients from the prospective Genomics of Chronic Allograft Rejection (GoCAR) study who underwent surveillance biopsies over 2 years, identifying those with subclinical or borderline acute cellular rejection (ACR) at 3 months (ACR-3) post-transplant. We performed RNA sequencing on whole blood collected from 88 individuals at the time of 3-month surveillance biopsy to identify transcripts associated with ACR-3, developed a novel sequencing-based targeted expression assay, and validated this gene signature in an independent cohort. Results Study participants with ACR-3 had significantly higher risk than those without ACR-3 of subsequent clinical acute rejection at 12 and 24 months, faster decline in graft function, and decreased graft survival in adjusted Cox analysis. We identified a 17-gene signature in peripheral blood that accurately diagnosed ACR-3, and validated it using microarray expression profiles of blood samples from 65 transplant recipients in the GoCAR cohort and three public microarray datasets. In an independent cohort of 110 transplant recipients, tests of the targeted expression assay on the basis of the 17-gene set showed that it identified individuals at higher risk of ongoing acute rejection and future graft loss. Conclusions Our targeted expression assay enabled noninvasive diagnosis of subclinical acute rejection and inflammation in the graft and may represent a useful tool to risk-stratify kidney transplant recipients. |
| Databáze: | OpenAIRE |
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