The Role of TGF-β in the Association Between Primary Graft Dysfunction and Bronchiolitis Obliterans Syndrome.
Journal Article (Clinical Trial;Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- DerHovanessian, A; Weigt, SS; Palchevskiy, V; Shino, MY; Sayah, DM; Gregson, AL; Noble, PW; Palmer, SM; Fishbein, MC; Kubak, BM; Ardehali, A; Ross, DJ; Saggar, R; Lynch, JP; Elashoff, RM; Belperio, JA
Published Date
- February 2016
Published In
Volume / Issue
- 16 / 2
Start / End Page
- 640 - 649
PubMed ID
- 26461171
Pubmed Central ID
- PMC4946573
Electronic International Standard Serial Number (EISSN)
- 1600-6143
Digital Object Identifier (DOI)
- 10.1111/ajt.13475
Language
- eng
Conference Location
- United States