title: Myocardial Gene Expression Profiling to Predict and Identify Cardiac Allograft Acute Cellular Rejection: The GET-Study.
abstract: OBJECTIVE
  Serial invasive endomyocardial biopsies (EMB) remain the gold standard for acute cellular rejection (ACR) diagnosis. However histological grading has several limitations. We aimed to explore the value of myocardial Gene Expression Profiling (GEP) for diagnosing and identifying predictive biomarkers of ACR.
  
  
  METHODS
  A case-control study nested within a retrospective heart transplant patients cohort included 126 patients with median (IQR) age 50 (41-57) years and 111 (88%) males. Among 1157 EMB performed, 467 were eligible (i.e, corresponding to either ISHLT grade 0 or ≥3A), among which 36 were selected for GEP according to the grading: 0 (CISHLT, n = 13); rejection ≥3A (RISHLT, n = 13); 0 one month before ACR (BRISHLT, n = 10).
  
  
  RESULTS
  We found 294 genes differentially expressed between CISHLT and RISHLT, mainly involved in immune activation, and inflammation. Hierarchical clustering showed a clear segregation of CISHLT and RISHLT groups and heterogeneity of GEP within RISHLT. All EMB presented immune activation, but some RISHLT EMB were strongly subject to inflammation, whereas others, closer to CISHLT, were characterized by structural modifications with lower inflammation level. We identified 15 probes significantly different between BRISHLT and CISHLT, including the gene of the muscular protein TTN. This result suggests that structural alterations precede inflammation in ACR. Linear Discriminant Analysis based on these 15 probes was able to identify the histological status of every 36 samples.
  
  
  CONCLUSIONS
  Myocardial GEP is a helpful method to accurately diagnose ACR, and predicts rejection one month before its histological occurrence. These results should be considered in cardiac allograft recipients' care.
authors.affiliation: AP-HP, Department of Cardiology, Henri Mondor Teaching Hospital, Créteil, France.|School of Medicine, Paris-Est-Créteil University (UPEC), Créteil, France.|IMRB INSERM U955, Paris-Est-Créteil University (UPEC), Créteil F-94000, France`.|DHU ATVB, Henri Mondor Teaching Hospital, Creteil, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Bodez
authors.affiliation: School of Medicine, Paris-Est-Créteil University (UPEC), Créteil, France.|IMRB INSERM U955, Paris-Est-Créteil University (UPEC), Créteil F-94000, France`.|Vaccine Research Institute (VRI), Henri Mondor Teaching Hospital, Créteil, France.
authors.forename: Hakim
authors.initials: H
authors.lastname: Hocini
authors.affiliation: CEA, DSV/iMETI, Immunology of viral infections and autoimmune diseases research unit, Fontenay-aux-Roses, France.|UMR1184, IDMIT infrastructure, Fontenay-aux-Roses, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tchitchek
authors.affiliation: School of Medicine, Paris-Est-Créteil University (UPEC), Créteil, France.|IMRB INSERM U955, Paris-Est-Créteil University (UPEC), Créteil F-94000, France`.|Vaccine Research Institute (VRI), Henri Mondor Teaching Hospital, Créteil, France.
authors.forename: Pascaline
authors.initials: P
authors.lastname: Tisserand
authors.affiliation: AP-HP, Department of Pathology, Henri Mondor Teaching Hospital, Créteil, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Benhaiem
authors.affiliation: School of Medicine, Paris-Est-Créteil University (UPEC), Créteil, France.|IMRB INSERM U955, Paris-Est-Créteil University (UPEC), Créteil F-94000, France`.|AP-HP, Platform of Biological Resources, Henri Mondor Teaching Hospital, Créteil, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Barau
authors.affiliation: AP-HP, Department of Cardiology, Henri Mondor Teaching Hospital, Créteil, France.|GRC Amyloid Research Institute, Henri Mondor Teaching Hospital, Créteil, France.
authors.forename: Mounira
authors.initials: M
authors.lastname: Kharoubi
authors.affiliation: AP-HP, Department of Cardiology, Henri Mondor Teaching Hospital, Créteil, France.|School of Medicine, Paris-Est-Créteil University (UPEC), Créteil, France.|IMRB INSERM U955, Paris-Est-Créteil University (UPEC), Créteil F-94000, France`.|DHU ATVB, Henri Mondor Teaching Hospital, Creteil, France.|GRC Amyloid Research Institute, Henri Mondor Teaching Hospital, Créteil, France.
authors.forename: Aziz
authors.initials: A
authors.lastname: Guellich
authors.affiliation: AP-HP, Department of Cardiology, Henri Mondor Teaching Hospital, Créteil, France.|School of Medicine, Paris-Est-Créteil University (UPEC), Créteil, France.|DHU ATVB, Henri Mondor Teaching Hospital, Creteil, France.|GRC Amyloid Research Institute, Henri Mondor Teaching Hospital, Créteil, France.
authors.forename: Soulef
authors.initials: S
authors.lastname: Guendouz
authors.affiliation: AP-HP, Department of Cardiac Surgery, Henri Mondor Teaching Hospital, Créteil, France.
authors.forename: Costin
authors.initials: C
authors.lastname: Radu
authors.affiliation: School of Medicine, Paris-Est-Créteil University (UPEC), Créteil, France.|IMRB INSERM U955, Paris-Est-Créteil University (UPEC), Créteil F-94000, France`.|AP-HP, Department of Cardiac Surgery, Henri Mondor Teaching Hospital, Créteil, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Couetil
authors.affiliation: School of Medicine, Paris-Est-Créteil University (UPEC), Créteil, France.|IMRB INSERM U955, Paris-Est-Créteil University (UPEC), Créteil F-94000, France`.|AP-HP, Platform of Biological Resources, Henri Mondor Teaching Hospital, Créteil, France.
authors.forename: Bijan
authors.initials: B
authors.lastname: Ghaleh
authors.affiliation: AP-HP, Department of Cardiology, Henri Mondor Teaching Hospital, Créteil, France.|School of Medicine, Paris-Est-Créteil University (UPEC), Créteil, France.|IMRB INSERM U955, Paris-Est-Créteil University (UPEC), Créteil F-94000, France`.|DHU ATVB, Henri Mondor Teaching Hospital, Creteil, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Dubois-Randé
authors.affiliation: AP-HP, Department of Cardiology, Henri Mondor Teaching Hospital, Créteil, France.|School of Medicine, Paris-Est-Créteil University (UPEC), Créteil, France.|IMRB INSERM U955, Paris-Est-Créteil University (UPEC), Créteil F-94000, France`.|DHU ATVB, Henri Mondor Teaching Hospital, Creteil, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Teiger
authors.affiliation: AP-HP, Department of Cardiology, Henri Mondor Teaching Hospital, Créteil, France.|School of Medicine, Paris-Est-Créteil University (UPEC), Créteil, France.|IMRB INSERM U955, Paris-Est-Créteil University (UPEC), Créteil F-94000, France`.|DHU ATVB, Henri Mondor Teaching Hospital, Creteil, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Hittinger
authors.affiliation: School of Medicine, Paris-Est-Créteil University (UPEC), Créteil, France.|IMRB INSERM U955, Paris-Est-Créteil University (UPEC), Créteil F-94000, France`.|Vaccine Research Institute (VRI), Henri Mondor Teaching Hospital, Créteil, France.|AP-HP, Clinical Immunology, Henri Mondor Teaching Hospital, Créteil, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Levy
authors.affiliation: AP-HP, Department of Cardiology, Henri Mondor Teaching Hospital, Créteil, France.|School of Medicine, Paris-Est-Créteil University (UPEC), Créteil, France.|IMRB INSERM U955, Paris-Est-Créteil University (UPEC), Créteil F-94000, France`.|DHU ATVB, Henri Mondor Teaching Hospital, Creteil, France.|GRC Amyloid Research Institute, Henri Mondor Teaching Hospital, Créteil, France.
authors.forename: Thibaud
authors.initials: T
authors.lastname: Damy
mesh_terms: D000328:Adult; D064591:Allografts; D015415:Biomarkers / 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; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D015415:Biomarkers