PLoS ONE (Jan 2011)

The chitinase-like protein YKL-40 modulates cystic fibrosis lung disease.

  • Andreas Hector,
  • Michael S D Kormann,
  • Ines Mack,
  • Philipp Latzin,
  • Carmen Casaulta,
  • Elisabeth Kieninger,
  • Zhe Zhou,
  • Ali Ö Yildirim,
  • Alexander Bohla,
  • Nikolaus Rieber,
  • Matthias Kappler,
  • Barbara Koller,
  • Ernst Eber,
  • Olaf Eickmeier,
  • Stefan Zielen,
  • Oliver Eickelberg,
  • Matthias Griese,
  • Marcus A Mall,
  • Dominik Hartl

DOI
https://doi.org/10.1371/journal.pone.0024399
Journal volume & issue
Vol. 6, no. 9
p. e24399

Abstract

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The chitinase-like protein YKL-40 was found to be increased in patients with severe asthma and chronic obstructive pulmonary disease (COPD), two disease conditions featuring neutrophilic infiltrates. Based on these studies and a previous report indicating that neutrophils secrete YKL-40, we hypothesized that YKL-40 plays a key role in cystic fibrosis (CF) lung disease, a prototypic neutrophilic disease. The aim of this study was (i) to analyze YKL-40 levels in human and murine CF lung disease and (ii) to investigate whether YKL-40 single-nucleotide polymorphisms (SNPs) modulate CF lung disease severity. YKL-40 protein levels were quantified in serum and sputum supernatants from CF patients and control individuals. Levels of the murine homologue BRP-39 were analyzed in airway fluids from CF-like βENaC-Tg mice. YKL-40SNPs were analyzed in CF patients. YKL-40 levels were increased in sputum supernatants and in serum from CF patients compared to healthy control individuals. Within CF patients, YKL-40 levels were higher in sputum than in serum. BRP-39 levels were increased in airways fluids from βENaC-Tg mice compared to wild-type littermates. In both CF patients and βENaC-Tg mice, YKL-40/BRP-39 airway levels correlated with the severity of pulmonary obstruction. Two YKL-40 SNPs (rs871799 and rs880633) were found to modulate age-adjusted lung function in CF patients. YKL-40/BRP-39 levelsare increased in human and murine CF airway fluids, correlate with pulmonary function and modulate CF lung disease severity genetically. These findings suggest YKL-40 as a potential biomarker in CF lung disease.