title: Receptor for advanced glycation end products in donor lungs is associated with primary graft dysfunction after lung transplantation.
abstract: Development of primary graft dysfunction (PGD) is associated with poor outcomes after transplantation. We hypothesized that Receptor for Advanced Glycation End-products (RAGE) levels in donor lungs is associated with the development of PGD. Furthermore, we hypothesized that RAGE levels would be increased with PGD in recipients after transplantation. We measured RAGE in bronchoalveolar lavage fluid (BALf) from 25 donors and 34 recipients. RAGE was also detected in biopsies (transbronchial biopsy) from recipients with and without PGD. RAGE levels were significantly higher in donor lungs that subsequently developed sustained PGD versus transplanted lungs that did not display PGD. Donor RAGE level was a predictor of recipient PGD (odds ratio = 1.768 per 0.25 ng/mL increase in donor RAGE level). In addition, RAGE levels remained high for 14 days in those recipients that developed severe graft dysfunction. Recipients may be at higher risk for developing PGD if they receive transplanted organs that have higher levels of soluble RAGE prior to explantation. Moreover, the clinical and pathologic abnormalities associated with PGD posttransplantation are associated with increased RAGE expression. These findings also raise the possibility that targeting the RAGE signaling pathway could be a novel strategy for treatment and/or prevention of PGD.
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA.|McKelvey Center for Lung Transplantation and Pulmonary Vascular Diseases, Emory University, Atlanta, GA.
authors.forename: A
authors.initials: A
authors.lastname: Pelaez
authors.affiliation: McKelvey Center for Lung Transplantation and Pulmonary Vascular Diseases, Emory University, Atlanta, GA.|Division of Cardiothoracic Surgery, Emory University, Atlanta, GA.
authors.forename: S D
authors.initials: SD
authors.lastname: Force
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University Hospital.
authors.forename: A A
authors.initials: AA
authors.lastname: Gal
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA.|McKelvey Center for Lung Transplantation and Pulmonary Vascular Diseases, Emory University, Atlanta, GA.
authors.forename: D C
authors.initials: DC
authors.lastname: Neujahr
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA.|McKelvey Center for Lung Transplantation and Pulmonary Vascular Diseases, Emory University, Atlanta, GA.
authors.forename: A M
authors.initials: AM
authors.lastname: Ramirez
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA.
authors.forename: P M
authors.initials: PM
authors.lastname: Naik
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA.
authors.forename: D A
authors.initials: DA
authors.lastname: Quintero
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA.
authors.forename: A V
authors.initials: AV
authors.lastname: Pileggi
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA.
authors.forename: K A
authors.initials: KA
authors.lastname: Easley
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA.
authors.forename: R
authors.initials: R
authors.lastname: Echeverry
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA.|McKelvey Center for Lung Transplantation and Pulmonary Vascular Diseases, Emory University, Atlanta, GA.
authors.forename: E C
authors.initials: EC
authors.lastname: Lawrence
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA.
authors.forename: D M
authors.initials: DM
authors.lastname: Guidot
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA.
authors.forename: P O
authors.initials: PO
authors.lastname: Mitchell
mesh_terms: D001706:Biopsy; D006084:Graft Rejection; D006801:Humans; D016040:Lung Transplantation; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D014019:Tissue Donors
chemical_list: D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic