title: Identification and classification of acute cardiac rejection by intragraft transcriptional profiling.
abstract: BACKGROUND
  Treatment of acute rejection (AR) in heart transplantation relies on histopathological grading of endomyocardial biopsies according to International Society for Heart and Lung Transplantation guidelines. Intragraft gene expression profiling may be a way to complement histological evaluation.
  
  
  RESULTS
  Transcriptional profiling was performed on 26 endomyocardial biopsies, and expression patterns were compared with the 1990 International Society for Heart and Lung Transplantation AR grades. Importantly, transcriptional profiles from settings with an equivalent AR grade appeared the same. In addition, grade 0 profiles could not be distinguished from 1A profiles, and grade 3A profiles could not be distinguished from 3B profiles. Comparing the AR groupings (0+1A, 1B, and 3A+3B), 0+1A showed more striking differences from 1B than from 3A+3B. When these findings were extrapolated to the 2005 revised guidelines, the combination of 1A and 1B into a single category (1R) appears to have brought together endomyocardial biopsies with different underlying processes that are not evident from histological evaluation. Grade 1B was associated with upregulated immune response genes, as 1 categorical distinction from grade 1A. Although grade 1B was distinct from the clinically relevant AR grades 3A and 3B, all of these grades shared a small number of overlapping pathways consistent with common physiological underpinnings.
  
  
  CONCLUSIONS
  The gene expression similarities and differences identified here in different AR settings have the potential to revise the clinical perspective on acute graft rejection, pending the results of larger studies.
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Cécile T J
authors.initials: CT
authors.lastname: Holweg
authors.forename: Luciano
authors.initials: L
authors.lastname: Potena
authors.forename: Helen
authors.initials: H
authors.lastname: Luikart
authors.forename: Tianwei
authors.initials: T
authors.lastname: Yu
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Berry
authors.forename: John P
authors.initials: JP
authors.lastname: Cooke
authors.forename: Hannah A
authors.initials: HA
authors.lastname: Valantine
authors.forename: Edward S
authors.initials: ES
authors.lastname: Mocarski
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D001706:Biopsy; D005260:Female; D020869:Gene Expression Profiling; D005820:Genetic Testing / Q000379:methods*; D006084:Graft Rejection / Q000145:classification / Q000235:genetics / Q000473:pathology; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D055815:Young Adult