A Common Peripheral Blood Gene Set for Diagnosis of Operational Tolerance in Pediatric and Adult Liver Transplantation

被引：86

作者：

Li, L. ^{[1
]}

Wozniak, L. J. ^{[2
]}

Rodder, S. ^{[1
]}

Heish, S. ^{[1
]}

Talisetti, A. ^{[3
]}

Wang, Q. ^{[1
]}

Esquivel, C. ^{[4
]}

Cox, K. ^{[3
]}

Chen, R. ^{[1
]}

McDiarmid, S. V. ^{[2
]}

Sarwal, M. M. ^{[1
,4
]}

机构：

[1] Stanford Univ, Dept Pediat, Div Nephrol, Palo Alto, CA 94304 USA

[2] Univ Calif Los Angeles, Dept Pediat, Div Gastroenterol, Los Angeles, CA 90024 USA

[3] Stanford Univ, Dept Pediat, Div Gastroenterol, Palo Alto, CA 94304 USA

[4] Calif Pacific Med Ctr Res Inst, San Francisco, CA USA

来源：

AMERICAN JOURNAL OF TRANSPLANTATION | 2012年 / 12卷 / 05期

关键词：

Biomarker diagnostics; liver transplantation; liver allograft tolerance; microarray gene expression; C VIRUS-INFECTION; HEPATITIS-C; IMMUNOSUPPRESSION WITHDRAWAL; T-CELLS; EXPRESSION; IDENTIFICATION; SIGNATURE; SELECTION;

D O I：

10.1111/j.1600-6143.2011.03928.x

中图分类号：

R61 [外科手术学];

学科分类号：

摘要：

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.

引用

页码：1218 / 1228

页数：11

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