title: The chitinase-like protein YKL-40 modulates cystic fibrosis lung disease.
abstract: 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.
authors.affiliation: Department I, Children's Hospital, University of Tübingen, Tübingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hector
authors.forename: Michael S D
authors.initials: MS
authors.lastname: Kormann
authors.forename: Ines
authors.initials: I
authors.lastname: Mack
authors.forename: Philipp
authors.initials: P
authors.lastname: Latzin
authors.forename: Carmen
authors.initials: C
authors.lastname: Casaulta
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kieninger
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhou
authors.forename: Ali Ö
authors.initials: AÖ
authors.lastname: Yildirim
authors.forename: Alexander
authors.initials: A
authors.lastname: Bohla
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Rieber
authors.forename: Matthias
authors.initials: M
authors.lastname: Kappler
authors.forename: Barbara
authors.initials: B
authors.lastname: Koller
authors.forename: Ernst
authors.initials: E
authors.lastname: Eber
authors.forename: Olaf
authors.initials: O
authors.lastname: Eickmeier
authors.forename: Stefan
authors.initials: S
authors.lastname: Zielen
authors.forename: Oliver
authors.initials: O
authors.lastname: Eickelberg
authors.forename: Matthias
authors.initials: M
authors.lastname: Griese
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Mall
authors.forename: Dominik
authors.initials: D
authors.lastname: Hartl
mesh_terms: D054392:Adipokines / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000071451:Chitinase-3-Like Protein 1; D003550:Cystic Fibrosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D037102:Lectins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D020641:Polymorphism, Single Nucleotide; D013183:Sputum / Q000378:metabolism; D055815:Young Adult
chemical_list: D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins