TY - JOUR
T1 - A common peripheral blood gene set for diagnosis of operational tolerance in pediatric and adult liver transplantation
AU - Li, L.
AU - Wozniak, L. J.
AU - Rodder, S.
AU - Heish, S.
AU - Talisetti, A.
AU - Wang, Q.
AU - Esquivel, C.
AU - Cox, K.
AU - Chen, R.
AU - McDiarmid, S. V.
AU - Sarwal, M. M.
PY - 2012/5
Y1 - 2012/5
N2 - 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. A peripheral blood QPCR-based algorithm based on the measurement of three gene transcripts can detect the acquisition of operational tolerance in children and adult recipients of liver transplants.
AB - 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. A peripheral blood QPCR-based algorithm based on the measurement of three gene transcripts can detect the acquisition of operational tolerance in children and adult recipients of liver transplants.
KW - Biomarker diagnostics
KW - liver allograft tolerance
KW - liver transplantation
KW - microarray gene expression
UR - http://www.scopus.com/inward/record.url?scp=84862783161&partnerID=8YFLogxK
U2 - 10.1111/j.1600-6143.2011.03928.x
DO - 10.1111/j.1600-6143.2011.03928.x
M3 - Article
C2 - 22300520
AN - SCOPUS:84862783161
SN - 1600-6135
VL - 12
SP - 1218
EP - 1228
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 5
ER -