title: Altered Exosomal RNA Profiles in Bronchoalveolar Lavage from Lung Transplants with Acute Rejection.
abstract: BACKGROUND
  The mechanism by which acute allograft rejection leads to chronic rejection remains poorly understood despite its common occurrence. Exosomes, membrane vesicles released from cells within the lung allograft, contain a diverse array of biomolecules that closely reflect the biologic state of the cell and tissue from which they are released. Exosome transcriptomes may provide a better understanding of the rejection process. Furthermore, biomarkers originating from this transcriptome could provide timely and sensitive detection of acute cellular rejection (AR), reducing the incidence of severe AR and chronic lung allograft dysfunction and improving outcomes.
  
  
  OBJECTIVE
  To provide an in-depth analysis of the bronchoalveolar lavage fluid exosomal shuttle RNA population after lung transplantation and evaluate for differential expression between acute AR and quiescence.
  
  
  METHODS
  Serial bronchoalveolar lavage specimens were ultracentrifuged to obtain the exosomal pellet for RNA extraction, on which RNA-Seq was performed.
  
  
  RESULTS
  AR demonstrates an intense inflammatory environment, skewed toward both innate and adaptive immune responses. Novel, potential upstream regulators identified offer potential therapeutic targets.
  
  
  CONCLUSIONS
  Our findings validate bronchoalveolar lavage fluid exosomal shuttle RNA as a source for understanding the pathophysiology of AR and for biomarker discovery in lung transplantation.
authors: 1 Division of Infectious Diseases, Department of Medicine.
authors: Aric L
authors: http://orcid.org/0000-0001-6806-0868
authors: AL
authors: Gregson
authors: 2 Department of Transplantation, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Aki
authors: A
authors: Hoji
authors: 3 Division of Pulmonary, Critical Care, Allergy, and Immunology, Department of Medicine, and.
authors: Patil
authors: P
authors: Injean
authors: 3 Division of Pulmonary, Critical Care, Allergy, and Immunology, Department of Medicine, and.
authors: Steven T
authors: ST
authors: Poynter
authors: 3 Division of Pulmonary, Critical Care, Allergy, and Immunology, Department of Medicine, and.
authors: Claudia
authors: C
authors: Briones
authors: 3 Division of Pulmonary, Critical Care, Allergy, and Immunology, Department of Medicine, and.
authors: Vyacheslav
authors: V
authors: Palchevskiy
authors: 3 Division of Pulmonary, Critical Care, Allergy, and Immunology, Department of Medicine, and.
authors: S Sam
authors: SS
authors: Weigt
authors: 3 Division of Pulmonary, Critical Care, Allergy, and Immunology, Department of Medicine, and.
authors: Michael Y
authors: MY
authors: Shino
authors: 3 Division of Pulmonary, Critical Care, Allergy, and Immunology, Department of Medicine, and.
authors: Ariss
authors: A
authors: Derhovanessian
authors: 3 Division of Pulmonary, Critical Care, Allergy, and Immunology, Department of Medicine, and.
authors: David
authors: http://orcid.org/0000-0001-7021-8273
authors: D
authors: Sayah
authors: 3 Division of Pulmonary, Critical Care, Allergy, and Immunology, Department of Medicine, and.
authors: Rajan
authors: R
authors: Saggar
authors: 3 Division of Pulmonary, Critical Care, Allergy, and Immunology, Department of Medicine, and.
authors: David
authors: D
authors: Ross
authors: 4 Division of Cardiothoracic Surgery, Department of Surgery, University of California, Los Angeles, California; and.
authors: Abbas
authors: A
authors: Ardehali
authors: 3 Division of Pulmonary, Critical Care, Allergy, and Immunology, Department of Medicine, and.
authors: Joseph P
authors: JP
authors: Lynch
authors: 3 Division of Pulmonary, Critical Care, Allergy, and Immunology, Department of Medicine, and.
authors: John A
authors: JA
authors: Belperio
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D055354:Exosomes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D008168:Lung / Q000276:immunology / Q000601:surgery; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000276:immunology*; D012313:RNA / Q000276:immunology*; D015203:Reproducibility of Results
chemical_list: D012313:RNA
keywords: RNA; exosome; rejection; lung; transplantation