A Common Peripheral Blood Gene Set for Diagnosis of Operational Tolerance in Pediatric and Adult Liver Transplantation
| Autor: | Kenneth L. Cox, Lulin Li, S. Rodder, S. Heish, Q. Wang, Rong Chen, S. V. McDiarmid, Anita Talisetti, Laura J. Wozniak, Minnie M. Sarwal, Carlos O. Esquivel |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Transcription Genetic Microarray medicine.medical_treatment Liver transplantation Real-Time Polymerase Chain Reaction Organ transplantation Predictive medicine Young Adult medicine Humans Immunology and Allergy Pharmacology (medical) RNA Messenger Child Oligonucleotide Array Sequence Analysis Transplantation Reverse Transcriptase Polymerase Chain Reaction business.industry Gene Expression Profiling Incidence (epidemiology) Infant Immunosuppression Phenotype Liver Transplantation Child Preschool Immunology Female Transplantation Tolerance business Biomarkers |
| Zdroj: | American Journal of Transplantation. 12:1218-1228 |
| ISSN: | 1600-6135 |
| DOI: | 10.1111/j.1600-6143.2011.03928.x |
| Popis: | To identify biomarkers of operational tolerance in pediatric and adult liver transplant recipients, transcriptional profiles were examined from 300 samples by microarrays and Q-PCR measurements of blood specimens from pediatric and adult liver transplant recipients and normal tissues. Tolerance-specific genes were validated in independent samples across two different transplant programs and validated by Q-PCR. A minimal set of 13 unique genes, highly expressed in natural killer cells (p = 0.03), were significantly expressed in both pediatric and adult liver tolerance, irrespective of different clinical and demographic confounders. The performance of this gene set by microarray in independent samples was 100% sensitivity and 83% specificity and the AUC was 0.988 for only three genes by Q-PCR. 26% of adults and 64% of children with excellent liver allograft function, on minimal or dual immunosuppression, showed high prediction scores for tolerance. Novel peripheral transcriptional profiles can be identified in operational tolerance in pediatric and adult recipients of liver allografts, suggesting a high incidence of a pro-tolerogenic phenotype in stable patients on chronic immunosuppression. Given the high incidence of viral infections and malignancies in liver transplant recipients, this gene set provides an important monitoring tool that can move the field toward personalized and predictive medicine in organ transplantation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text