Circulating fibrocytes as biomarker of prognosis in Hermansky-Pudlak syndrome.

Abstract:

RATIONALE: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. OBJECTIVES: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. MEASUREMENTS AND MAIN 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

Trimble A,Gochuico BR,Markello TC,Fischer R,Gahl WA,Lee JK,Kim Y,Burdick MD,Strieter RM,Mehrad B

doi

10.1164/rccm.201407-1287OC

subject

Has Abstract

pub_date

2014-12-15 00:00:00

pages

1395-401

issue

12

eissn

1073-449X

issn

1535-4970

journal_volume

190

pub_type

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