Cumulative exposure to gamma interferon-dependent chemokines CXCL9 and CXCL10 correlates with worse outcome after lung transplant.

Journal Article (Journal Article)

Outcomes following lung transplant are suboptimal owing to chronic allograft failure termed bronchiolitis obliterans syndrome (BOS). Prior work in both mice and humans has shown that interferon gamma (IFNG)-induced chemokines, including CXCL9 and CXCL10, are elevated in patients with established BOS. We hypothesized that patients who ultimately developed BOS would have elevations in these chemokines before losing lung function. We utilized a high throughput multiplex enzyme-linked immunosorbent assay (ELISA) to measure biomarkers in bronchoalveolar lavage fluid (BALF). We modeled cumulative exposure to seven biomarkers (CXCL9, CXCL10, RANTES, IL1-RA, IL-17, MCP1 and IL-13) by calculating the 1-year area under the curve (AUC) for each biomarker in the BALF of 40 lung transplant patients who had at least four samples obtained in the first year posttransplant. Cumulative elevations in CXCL9 and CXCL10 were associated with a significant risk of subsequent graft failure after transplant (HR 9.37 and 5.52, respectively; p < 0.01 for both). Further these chemokines were also elevated in patients before the onset of BOS. CXCL9 and CXCL10 elevations were seen between 3 and 9 months before graft failure. Our data show that persistent presence of CXCL9 and CXCL10 portents worsening lung allograft function; measuring these IFNG-induced chemokines might prospectively identify patients at risk for BOS.

Full Text

Duke Authors

Cited Authors

  • Neujahr, DC; Perez, SD; Mohammed, A; Ulukpo, O; Lawrence, EC; Fernandez, F; Pickens, A; Force, SD; Song, M; Larsen, CP; Kirk, AD

Published Date

  • February 2012

Published In

Volume / Issue

  • 12 / 2

Start / End Page

  • 438 - 446

PubMed ID

  • 22151926

Pubmed Central ID

  • PMC3395060

Electronic International Standard Serial Number (EISSN)

  • 1600-6143

Digital Object Identifier (DOI)

  • 10.1111/j.1600-6143.2011.03857.x


  • eng

Conference Location

  • United States