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

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.