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Transcriptional signals of T-cell and corticosteroid-sensitive genes are associated with future acute cellular rejection in cardiac allografts
Journal article   Peer reviewed

Transcriptional signals of T-cell and corticosteroid-sensitive genes are associated with future acute cellular rejection in cardiac allografts

Mandeep R. Mehra, Jon A. Kobashigawa, Mario C. Deng, Kenneth C. Fang, Tod M. Klingler, Preeti G. Lal, Steven Rosenberg, Patricia A. Uber, Randall C. Starling, Srinivas Murali, …
The Journal of heart and lung transplantation, v 26(12), pp 1255-1263
01 Dec 2007
PMID: 18096476

Abstract

Cardiac & Cardiovascular Systems Cardiovascular System & Cardiology Life Sciences & Biomedicine Respiratory System Science & Technology Surgery Transplantation
Background: Profiling mRNA levels of I I informative genes expressed by circulating immune effector cells identifies cardiac allograft recipients at low risk for current moderate-severe acute cellular rejection (ACR). Methods: We conducted a nested case-control study of 104 cardiac allograft recipients to investigate the association of transcriptional profiles of blood samples with either a future rejection episode within 12 weeks of a baseline clinical sample or persistent histologic quiescence for the same time period. Results: The transcription profile yielded a score (0 to 40 scale) of 27.4 +/- 6.3 for future rejectors (n = 39) and 23.9 +/- 7.1 for controls (n = 65) (p = 0.01). In patients who were <= 180 days post-transplant, the gene expression score was 28.4 +/- 4.9 for rejectors (n = 28) and 22.4 +/- 7.5 for controls (n = 48) (p < 0.001). In this period, no samples from patients who went on to reject within 12 weeks had gene expression scores of <20. Differential expression of the gene IL1R2 was significantly associated with future events. Of 33 additional genes profiled, 5 supported corticosteroid-sensitive constituents (lL1R2 and FLT3), whereas 6 supported T-cell activation (PDCD1). Conclusions: These data suggest that pathways regulating T-cell homeostasis and corticosteroid sensitivity are associated with future ACR in cardiac allografts and suggest that these signals are evident before histologically detectable rejection. J Heart Lung Transplant 2007;26:1255-63. Copyright (c) 2007 by the International Society for Heart and Lung Transplantation.

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Collaboration types
Domestic collaboration
Web of Science research areas
Cardiac & Cardiovascular Systems
Respiratory System
Surgery
Transplantation
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