title: Circulating fibrocytes as biomarker of prognosis in Hermansky-Pudlak syndrome.
abstract: BACKGROUND
  The rate of progression of most interstitial lung diseases (ILD) is unpredictable. Fibrocytes are circulating bone marrow-derived cells that have been implicated in the pathogenesis of lung fibrosis. Hermansky-Pudlak syndrome (HPS), a genetic cause of ILD in early adulthood, allows for study of biomarkers of ILD in a homogeneous population at near-certain risk of developing fibrotic lung disease.
  
  
  OBJECTIVE
  To test the hypothesis that, in subjects with HPS, the number or phenotype of circulating fibrocytes predicts progression and outcome of ILD.
  
  
  METHODS
  We measured circulating fibrocyte counts and chemokine levels in a cohort of subjects with HPS and healthy control subjects and correlated the results to disease outcome.
  
  
  RESULTS
  In a cross-sectional analysis, peripheral blood fibrocyte concentrations were markedly elevated in a subset of subjects with HPS who had ILD but not subjects without lung disease or normal control subjects. The blood concentration of fibrocytes expressing the chemokine receptor CXCR4 correlated significantly with the plasma concentration of the CXCR4 ligand, CXCL12. In a longitudinal study, we found marked episodic elevations in circulating fibrocyte counts over a median follow-up period of 614 days. Elevations in both maximal values and final values of peripheral blood CXCR4(+) fibrocyte concentration were strongly associated with death from ILD.
  
  
  CONCLUSIONS
  CXCR4(+) fibrocyte concentration may be useful as a biomarker for outcome of ILD in subjects with HPS.
authors.affiliation: 1 Department of Medicine and.
authors.forename: Aaron
authors.initials: A
authors.lastname: Trimble
authors.forename: Bernadette R
authors.initials: BR
authors.lastname: Gochuico
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Markello
authors.forename: Roxanne
authors.initials: R
authors.lastname: Fischer
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
authors.forename: Jae K
authors.initials: JK
authors.lastname: Lee
authors.forename: Youngchul
authors.initials: Y
authors.lastname: Kim
authors.forename: Marie D
authors.initials: MD
authors.lastname: Burdick
authors.forename: Robert M
authors.initials: RM
authors.lastname: Strieter
authors.forename: Borna
authors.initials: B
authors.lastname: Mehrad
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D022861:Hermanski-Pudlak Syndrome / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008875:Middle Aged; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000097:blood / Q000502:physiology; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4
keywords: CXCR4 receptors; chemokines; interstitial lung diseases; stem cells