title: Peripheral Blood Gene Expression Changes Associated With Primary Graft Dysfunction After Lung Transplantation.
abstract: Recipient responses to primary graft dysfunction (PGD) after lung transplantation may have important implications to the fate of the allograft. We therefore evaluated longitudinal differences in peripheral blood gene expression in subjects with PGD. RNA expression was measured throughout the first transplant year in 106 subjects enrolled in the Clinical Trials in Organ Transplantation-03 study using a panel of 100 hypothesis-driven genes. PGD was defined as grade 3 in the first 72 posttransplant hours. Eighteen genes were differentially expressed over the first year based on PGD development, with significant representation from innate and adaptive immunity genes, with most differences identified very early after transplant. Sixteen genes were overexpressed in the blood of patients with PGD compared to those without PGD within 7 days of allograft reperfusion, with most transcripts encoding innate immune/inflammasome-related proteins, including genes previously associated with PGD. Thirteen genes were underexpressed in patients with PGD compared to those without PGD within 7 days of transplant, highlighted by T cell and adaptive immune regulation genes. Differences in gene expression present within 2 h of reperfusion and persist for days after transplant. Future investigation will focus on the long-term implications of these gene expression differences on the outcome of the allograft.
authors.affiliation: Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors.forename: J M
authors.initials: JM
authors.lastname: Diamond
authors.affiliation: Division of Cardiovascular Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors.forename: E
authors.initials: E
authors.lastname: Cantu
authors.affiliation: Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors.forename: M K
authors.initials: MK
authors.lastname: Porteous
authors.affiliation: Division of Cardiovascular Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: K C
authors.initials: KC
authors.lastname: Meyer
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: D J
authors.initials: DJ
authors.lastname: Lederer
authors.affiliation: Division of Cardiovascular Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors.forename: R K
authors.initials: RK
authors.lastname: Milewski
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: S
authors.initials: S
authors.lastname: Arcasoy
authors.affiliation: Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: F
authors.initials: F
authors.lastname: D'Ovidio
authors.affiliation: Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: M
authors.initials: M
authors.lastname: Bacchetta
authors.affiliation: Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: J R
authors.initials: JR
authors.lastname: Sonett
authors.affiliation: Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: G
authors.initials: G
authors.lastname: Singh
authors.affiliation: Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: J
authors.initials: J
authors.lastname: Costa
authors.affiliation: Penn Molecular Profiling Facility, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: J W
authors.initials: JW
authors.lastname: Tobias
authors.affiliation: Penn Molecular Profiling Facility, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: H
authors.initials: H
authors.lastname: Rodriguez
authors.affiliation: Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors.forename: V M
authors.initials: VM
authors.lastname: Van Deerlin
authors.affiliation: Penn Transplant Institute, Hospital of the University of Pennsylvania, Philadelphia, PA.
authors.forename: K M
authors.initials: KM
authors.lastname: Olthoff
authors.affiliation: Penn Transplant Institute, Hospital of the University of Pennsylvania, Philadelphia, PA.
authors.forename: A
authors.initials: A
authors.lastname: Shaked
authors.affiliation: Penn Transplant Institute, Hospital of the University of Pennsylvania, Philadelphia, PA.|The Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: B-L
authors.initials: BL
authors.lastname: Chang
authors.affiliation: Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors.forename: J D
authors.initials: JD
authors.lastname: Christie
mesh_terms: D064591:Allografts; D015415:Biomarkers / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D055031:Primary Graft Dysfunction / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers
keywords: genomics; lung failure/injury; lung transplantation/pulmonology; molecular biology: mRNA/mRNA expression; translational research/science