title: Early prognosis of the development of renal chronic allograft rejection by gene expression profiling of human protocol biopsies.
abstract: BACKGROUND
  Chronic allograft rejection (CR) is the major cause of failure of long-term graft survival and is so far irreversible. Early prognosis of CR by molecular markers before overt histologic manifestation would be a valuable aid for the optimization of treatment regimens and the design of clinical CR trials. Oligonucleotide microarray-based approaches have proven to be useful for the diagnosis and prognosis of a variety of diseases and were chosen for the unbiased identification of prognostic biomarkers.
  
  
  METHODS
  Renal allograft biopsies were taken at month 6 posttransplantation (PT) from two groups who were, at that time, healthy recipients: one group developed CR at month-12 PT, the other group remained healthy. Gene expression profiles from the two groups at month-6 PT biopsies were analyzed to identify differentially expressed genes with prognostic value for CR development at month 12.
  
  
  RESULTS
  A set of 10 genes was identified that showed differential expression profiles between the two patient groups and had a complete separation of the 15% to 85% quantile range for each individual gene. This set of genes was sufficient to allow the correct prediction of the occurrence or nonoccurrence of CR in 15 of 17 (88%) patients using cross-validation (occurrence for a patient was predicted on the basis of the other patients' data only). In addition, a correct prediction could be made that a recipient with a normal biopsy 12 months PT developed CR within the following 6 months.
  
  
  CONCLUSIONS
  Identified expression patterns seem to be highly prognostic of the development of renal CR.
authors.affiliation: Novartis Institutes for BioMedical Research/Transplantation, Novartis Pharma AG, Basel, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Scherer
authors.forename: Andreas
authors.initials: A
authors.lastname: Krause
authors.forename: John R
authors.initials: JR
authors.lastname: Walker
authors.forename: Alexander
authors.initials: A
authors.lastname: Korn
authors.forename: Detlef
authors.initials: D
authors.lastname: Niese
authors.forename: Friedrich
authors.initials: F
authors.lastname: Raulf
mesh_terms: D000328:Adult; D001706:Biopsy; D002908:Chronic Disease; D005260:Female; D020869:Gene Expression Profiling; D006084:Graft Rejection; D006801:Humans; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012016:Reference Values; D013997:Time Factors; D014184:Transplantation, Homologous