title: Gene Expression Profiling of Bronchoalveolar Lavage Cells Preceding a Clinical Diagnosis of Chronic Lung Allograft Dysfunction.
abstract: BACKGROUND
  Chronic Lung Allograft Dysfunction (CLAD) is the main limitation to long-term survival after lung transplantation. Although CLAD is usually not responsive to treatment, earlier identification may improve treatment prospects.
  
  
  METHODS
  In a nested case control study, 1-year post transplant surveillance bronchoalveolar lavage (BAL) fluid samples were obtained from incipient CLAD (n = 9) and CLAD free (n = 8) lung transplant recipients. Incipient CLAD cases were diagnosed with CLAD within 2 years, while controls were free from CLAD for at least 4 years following bronchoscopy. Transcription profiles in the BAL cell pellets were assayed with the HG-U133 Plus 2.0 microarray (Affymetrix). Differential gene expression analysis, based on an absolute fold change (incipient CLAD vs no CLAD) >2.0 and an unadjusted p-value ≤0.05, generated a candidate list containing 55 differentially expressed probe sets (51 up-regulated, 4 down-regulated).
  
  
  RESULTS
  The cell pellets in incipient CLAD cases were skewed toward immune response pathways, dominated by genes related to recruitment, retention, activation and proliferation of cytotoxic lymphocytes (CD8+ T-cells and natural killer cells). Both hierarchical clustering and a supervised machine learning tool were able to correctly categorize most samples (82.3% and 94.1% respectively) into incipient CLAD and CLAD-free categories.
  
  
  CONCLUSIONS
  These findings suggest that a pathobiology, similar to AR, precedes a clinical diagnosis of CLAD. A larger prospective investigation of the BAL cell pellet transcriptome as a biomarker for CLAD risk stratification is warranted.
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, United States of America.
authors.forename: S Samuel
authors.identifier: http://orcid.org/0000-0001-5351-8936
authors.initials: SS
authors.lastname: Weigt
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, United States of America.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, United States of America.
authors.forename: Vyacheslav
authors.initials: V
authors.lastname: Palchevskiy
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, United States of America.
authors.forename: Aric L
authors.initials: AL
authors.lastname: Gregson
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, United States of America.
authors.forename: Naman
authors.initials: N
authors.lastname: Patel
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, United States of America.
authors.forename: Ariss
authors.initials: A
authors.lastname: DerHovanessian
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, United States of America.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Shino
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, United States of America.
authors.forename: David M
authors.initials: DM
authors.lastname: Sayah
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, United States of America.
authors.forename: Shirin
authors.initials: S
authors.lastname: Birjandi
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, United States of America.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Lynch
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, United States of America.
authors.forename: Rajan
authors.initials: R
authors.lastname: Saggar
authors.affiliation: Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, California, United States of America.
authors.forename: Abbas
authors.initials: A
authors.lastname: Ardehali
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Ross
authors.affiliation: Department of Medicine, Duke University, Durham, North Carolina, United States of America.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Palmer
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, United States of America.
authors.forename: John A
authors.initials: JA
authors.lastname: Belperio
mesh_terms: D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D006084:Graft Rejection / Q000235:genetics*; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis