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, Daniel F. Pauly, Russell Dedrick, Michael G. Walker, Adriana Zeevi, Howard J. Eisen

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21 Scopus citations

Abstract

Background: Profiling mRNA levels of 11 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 (IL1R2 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.

Original languageEnglish (US)
Pages (from-to)1255-1263
Number of pages9
JournalJournal of Heart and Lung Transplantation
Volume26
Issue number12
DOIs
StatePublished - Dec 2007

All Science Journal Classification (ASJC) codes

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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    Mehra, M. R., Kobashigawa, J. A., Deng, M. C., Fang, K. C., Klingler, T. M., Lal, P. G., Rosenberg, S., Uber, P. A., Starling, R. C., Murali, S., Pauly, D. F., Dedrick, R., Walker, M. G., Zeevi, A., & Eisen, H. J. (2007). Transcriptional Signals of T-cell and Corticosteroid-sensitive Genes Are Associated With Future Acute Cellular Rejection in Cardiac Allografts. Journal of Heart and Lung Transplantation, 26(12), 1255-1263. https://doi.org/10.1016/j.healun.2007.09.009