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The Role of TGF-β in the Association Between Primary Graft Dysfunction and Bronchiolitis Obliterans Syndrome.
Am J Transplant 2016; 16(2):640-9AJ

Abstract

Primary graft dysfunction (PGD) is a possible risk factor for bronchiolitis obliterans syndrome (BOS) following lung transplantation; however, the mechanism for any such association is poorly understood. Based on the association of TGF-β with acute and chronic inflammatory disorders, we hypothesized that it might play a role in the continuum between PGD and BOS. Thus, the association between PGD and BOS was assessed in a single-center cohort of lung transplant recipients. Bronchoalveolar lavage fluid concentrations of TGF-β and procollagen collected within 24 h of transplantation were compared across the spectrum of PGD, and incorporated into Cox models of BOS. Immunohistochemistry localized expression of TGF-β and its receptor in early lung biopsies posttransplant. We found an association between PGD and BOS in both bilateral and single lung recipients with a hazard ratio of 3.07 (95% CI 1.76-5.38) for the most severe form of PGD. TGF-β and procollagen concentrations were elevated during PGD (p < 0.01), and associated with increased rates of BOS. Expression of TGF-β and its receptor localized to allograft infiltrating mononuclear and stromal cells, and the airway epithelium. These findings validate the association between PGD and the subsequent development of BOS, and suggest that this association may be mediated by receptor/TGF-β biology.

Authors+Show Affiliations

Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Los Angeles, CA.Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Los Angeles, CA.Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Los Angeles, CA.Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Los Angeles, CA.Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Los Angeles, CA.Division of Infectious Diseases, Department of Medicine, University of California, Los Angeles, CA.Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA.Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University, Durham, NC.Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA.Division of Infectious Diseases, Department of Medicine, University of California, Los Angeles, CA.Division of Cardiothoracic Surgery, Department of Surgery, University of California, Los Angeles, CA.Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Los Angeles, CA.Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Los Angeles, CA.Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Los Angeles, CA.Department of Biomathematics, University of California, Los Angeles, CA.Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Los Angeles, CA.

Pub Type(s)

Clinical Trial
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

26461171

Citation

DerHovanessian, A, et al. "The Role of TGF-β in the Association Between Primary Graft Dysfunction and Bronchiolitis Obliterans Syndrome." American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, vol. 16, no. 2, 2016, pp. 640-9.
DerHovanessian A, Weigt SS, Palchevskiy V, et al. The Role of TGF-β in the Association Between Primary Graft Dysfunction and Bronchiolitis Obliterans Syndrome. Am J Transplant. 2016;16(2):640-9.
DerHovanessian, A., Weigt, S. S., Palchevskiy, V., Shino, M. Y., Sayah, D. M., Gregson, A. L., ... Belperio, J. A. (2016). The Role of TGF-β in the Association Between Primary Graft Dysfunction and Bronchiolitis Obliterans Syndrome. American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 16(2), pp. 640-9. doi:10.1111/ajt.13475.
DerHovanessian A, et al. The Role of TGF-β in the Association Between Primary Graft Dysfunction and Bronchiolitis Obliterans Syndrome. Am J Transplant. 2016;16(2):640-9. PubMed PMID: 26461171.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Role of TGF-β in the Association Between Primary Graft Dysfunction and Bronchiolitis Obliterans Syndrome. AU - DerHovanessian,A, AU - Weigt,S S, AU - Palchevskiy,V, AU - Shino,M Y, AU - Sayah,D M, AU - Gregson,A L, AU - Noble,P W, AU - Palmer,S M, AU - Fishbein,M C, AU - Kubak,B M, AU - Ardehali,A, AU - Ross,D J, AU - Saggar,R, AU - Lynch,J P,3rd AU - Elashoff,R M, AU - Belperio,J A, Y1 - 2015/10/13/ PY - 2015/01/11/received PY - 2015/06/09/revised PY - 2015/07/03/accepted PY - 2015/10/14/entrez PY - 2015/10/16/pubmed PY - 2016/11/12/medline SP - 640 EP - 9 JF - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons JO - Am. J. Transplant. VL - 16 IS - 2 N2 - Primary graft dysfunction (PGD) is a possible risk factor for bronchiolitis obliterans syndrome (BOS) following lung transplantation; however, the mechanism for any such association is poorly understood. Based on the association of TGF-β with acute and chronic inflammatory disorders, we hypothesized that it might play a role in the continuum between PGD and BOS. Thus, the association between PGD and BOS was assessed in a single-center cohort of lung transplant recipients. Bronchoalveolar lavage fluid concentrations of TGF-β and procollagen collected within 24 h of transplantation were compared across the spectrum of PGD, and incorporated into Cox models of BOS. Immunohistochemistry localized expression of TGF-β and its receptor in early lung biopsies posttransplant. We found an association between PGD and BOS in both bilateral and single lung recipients with a hazard ratio of 3.07 (95% CI 1.76-5.38) for the most severe form of PGD. TGF-β and procollagen concentrations were elevated during PGD (p < 0.01), and associated with increased rates of BOS. Expression of TGF-β and its receptor localized to allograft infiltrating mononuclear and stromal cells, and the airway epithelium. These findings validate the association between PGD and the subsequent development of BOS, and suggest that this association may be mediated by receptor/TGF-β biology. SN - 1600-6143 UR - https://www.unboundmedicine.com/medline/citation/26461171/The_Role_of_TGF_β_in_the_Association_Between_Primary_Graft_Dysfunction_and_Bronchiolitis_Obliterans_Syndrome_ L2 - https://doi.org/10.1111/ajt.13475 DB - PRIME DP - Unbound Medicine ER -