title: Transcriptional signals of T-cell and corticosteroid-sensitive genes are associated with future acute cellular rejection in cardiac allografts.
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 <or=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.
authors: Division of Cardiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. mmehra@medicine.umaryland.edu
authors: Mandeep R
authors: MR
authors: Mehra
authors: Jon A
authors: JA
authors: Kobashigawa
authors: Mario C
authors: MC
authors: Deng
authors: Kenneth C
authors: KC
authors: Fang
authors: Tod M
authors: TM
authors: Klingler
authors: Preeti G
authors: PG
authors: Lal
authors: Steven
authors: S
authors: Rosenberg
authors: Patricia A
authors: PA
authors: Uber
authors: Randall C
authors: RC
authors: Starling
authors: Srinivas
authors: S
authors: Murali
authors: Daniel F
authors: DF
authors: Pauly
authors: Russell
authors: R
authors: Dedrick
authors: Michael G
authors: MG
authors: Walker
authors: Adriana
authors: A
authors: Zeevi
authors: Howard J
authors: HJ
authors: Eisen
mesh_terms: D000305:Adrenal Cortex Hormones / Q000502:physiology; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D001706:Biopsy; D039481:CD11b Antigen / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D006084:Graft Rejection / Q000175:diagnosis* / Q000235:genetics*; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009206:Myocardium / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger / Q000235:genetics; D053574:Receptors, Interleukin-1 Type II / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology; D051941:fms-Like Tyrosine Kinase 3 / Q000097:blood / Q000235:genetics* / Q000378:metabolism
chemical_list: D000305:Adrenal Cortex Hormones; D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D039481:CD11b Antigen; C508592:IL1R2 protein, human; C509295:ITGAM protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger; D053574:Receptors, Interleukin-1 Type II; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3