title: Cumulative exposure to gamma interferon-dependent chemokines CXCL9 and CXCL10 correlates with worse outcome after lung transplant.
abstract: 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.
authors.affiliation: Emory Transplant Center, Emory University School of Medicine, Atlanta, GA, USA. David.neujahr@emoryhealthcare.org
authors.forename: D C
authors.initials: DC
authors.lastname: Neujahr
authors.forename: S D
authors.initials: SD
authors.lastname: Perez
authors.forename: A
authors.initials: A
authors.lastname: Mohammed
authors.forename: O
authors.initials: O
authors.lastname: Ulukpo
authors.forename: E C
authors.initials: EC
authors.lastname: Lawrence
authors.forename: F
authors.initials: F
authors.lastname: Fernandez
authors.forename: A
authors.initials: A
authors.lastname: Pickens
authors.forename: S D
authors.initials: SD
authors.lastname: Force
authors.forename: M
authors.initials: M
authors.lastname: Song
authors.forename: C P
authors.initials: CP
authors.lastname: Larsen
authors.forename: A D
authors.initials: AD
authors.lastname: Kirk
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001989:Bronchiolitis Obliterans / Q000378:metabolism / Q000601:surgery*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D054357:Chemokine CXCL10 / Q000378:metabolism*; D054370:Chemokine CXCL9 / Q000378:metabolism*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000378:metabolism*; D006085:Graft Survival; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D011379:Prognosis; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D007371:Interferon-gamma