A Five-Gene Peripheral Blood Diagnostic Test for Acute Rejection in Renal Transplantation
| Autor: | Vikas R. Dharnidharka, Amery Chen, Tara K. Sigdel, David B. Kershaw, M. Zhang, Minnie M. Sarwal, Bradley A. Warady, Rong Chen, Robert B. Ettenger, Oscar Salvatierra, Ruth A. McDonald, V. M. Vehaskari, Hong Dai, Tim Q. Tran, Szu-Chuan Hsieh, M. Vitalone, Valeriya Zarkhin, Rasika A. Mathias, Poonam Sansanwal, Wenzhong Xiao, Purvesh Khatri, M. Benfield, Anthony A. Portale, Maarten Naesens, Ronald W. Davis, Lihua Ying, Atul J. Butte, Michael N. Mindrinos, H. J. Baluarte, Li Li, Elaine S. Kamil, William E. Harmon |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Oncology
Graft Rejection Pathology Kidney Disease Single Center Polymerase Chain Reaction Medical and Health Sciences Acute allograft rejection Immunology and Allergy Medicine Pharmacology (medical) Prospective cohort study Kidney transplantation Pediatric screening and diagnosis medicine.diagnostic_test transplant rejection bioinformatics renal transplantation Transplant rejection Detection Acute Disease biomarker Biomarker (medicine) Renal biopsy Biotechnology 4.2 Evaluation of markers and technologies medicine.medical_specialty Renal and urogenital Sensitivity and Specificity renal allograft rejection Article Rare Diseases Clinical Research Internal medicine Biopsy Genetics Humans Transplantation business.industry Organ Transplantation medicine.disease Kidney Transplantation 4.1 Discovery and preclinical testing of markers and technologies transplantation genomics translational research Surgery business |
| Zdroj: | American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, vol 12, iss 10 |
| Popis: | Monitoring of renal graft status through peripheral blood (PB) rather than invasive biopsy is important as it will lessen the risk of infection and other stresses, while reducing the costs of rejection diagnosis. Blood gene biomarker panels were discovered by microarrays at a single center and subsequently validated and cross-validated by QPCR in the NIH SNSO1 randomized study from 12 US pediatric transplant programs. A total of 367 unique human PB samples, each paired with a graft biopsy for centralized, blinded phenotype classification, were analyzed (115 acute rejection (AR), 180 stable and 72 other causes of graft injury). Of the differentially expressed genes by microarray, Q-PCR analysis of a five gene-set (DUSP1, PBEF1, PSEN1, MAPK9 and NKTR) classified AR with high accuracy. A logistic regression model was built on independent training-set (n = 47) and validated on independent test-set (n = 198)samples, discriminating AR from STA with 91% sensitivity and 94% specificity and AR from all other non-AR phenotypes with 91% sensitivity and 90% specificity. The 5-gene set can diagnose AR potentially avoiding the need for invasive renal biopsy. These data support the conduct of a prospective study to validate the clinical predictive utility of this diagnostic tool. |
| Databáze: | OpenAIRE |
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