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

Hector, Andreas; Kormann, Michael S D; Mack, Ines; Latzin, Philipp; Casaulta, Carmen; Kieninger, Elisabeth; Zhou, Zhe; Yildirim, Ali Ö; Bohla, Alexander; Rieber, Nikolaus; Kappler, Matthias; Koller, Barbara; Eber, Ernst; Eickmeier, Olaf; Zielen, Stefan; Eickelberg, Oliver; Griese, Matthias; Mall, Marcus A; Hartl, Dominik (2011). The chitinase-like protein YKL-40 modulates cystic fibrosis lung disease. PLoS ONE, 6(9), e24399. Lawrence, Kans.: Public Library of Science 10.1371/journal.pone.0024399

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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.

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