title: Fucosylated surfactant protein-D is a biomarker candidate for the development of chronic obstructive pulmonary disease.
abstract: We previously reported that knockout mice for α1,6-fucosyltransferase (Fut8), which catalyzes the biosynthesis of core-fucose in N-glycans, develop emphysema and that Fut8 heterozygous knockout mice are more sensitive to cigarette smoke-induced emphysema than wild-type mice. Moreover, a lower FUT8 activity was found to be associated with a faster decline in lung function among chronic obstructive pulmonary disease (COPD) patients. These results led us to hypothesize that core-fucosylation levels in a glycoprotein could be used as a biomarker for COPD. We focused on a lung-specific glycoprotein, surfactant protein D (SP-D), which plays a role in immune responses and is present in the distal airways, alveoli, and blood circulation. The results of a glycomic analysis reported herein demonstrate the presence of a core-fucose in an N-glycan on enriched SP-D from pooled human sera. We developed an antibody-lectin enzyme immunoassay (EIA) for assessing fucosylation (core-fucose and α1,3/4 fucose) in COPD patients. The results indicate that fucosylation levels in serum SP-D are significantly higher in COPD patients than in non-COPD smokers. The severity of emphysema was positively associated with fucosylation levels in serum SP-D in smokers. Our findings suggest that increased fucosylation levels in serum SP-D are associated with the development of COPD.
  
  
  CONCLUSIONS
  It has been proposed that serum SP-D concentrations are predictive of COPD pathogenesis, but distinguishing between COPD patients and healthy individuals to establish a clear cut-off value is difficult because smoking status highly affects circulating SP-D levels. Herein, we focused on N-glycosylation in SP-D and examined whether or not N-glycosylation patterns in SP-D are associated with the pathogenesis of COPD. We performed an N-glycomic analysis of human serum SP-D and the results show that a core-fucose is present in its N-glycan. We also found that the N-glycosylation in serum SP-D was indeed altered in COPD, that is, fucosylation levels including core-fucosylation are significantly increased in COPD patients compared with non-COPD smokers. The severity of emphysema was positively associated with fucosylation levels in serum SP-D in smokers. Our findings shed new light on the discovery and/or development of a useful biomarker based on glycosylation changes for diagnosing COPD. This article is part of a Special Issue entitled: HUPO 2014.
authors.affiliation: Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center, RIKEN Global Research Cluster, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Ito
authors.affiliation: Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center, RIKEN Global Research Cluster, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Oka
authors.affiliation: Respiratory Care Clinic, Nippon Medical School, 4-7-15-8F Kudan-Minami, Chiyoda-ku, Tokyo 102-0074, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Ishii
authors.affiliation: Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center, RIKEN Global Research Cluster, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan. Electronic address: korekane@sanken.osaka-u.ac.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Korekane
authors.affiliation: Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center, RIKEN Global Research Cluster, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Kurimoto
authors.affiliation: Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center, RIKEN Global Research Cluster, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kizuka
authors.affiliation: Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center, RIKEN Global Research Cluster, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Kitazume
authors.affiliation: Department of Biochemistry, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ariki
authors.affiliation: Department of Biochemistry, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Biochemistry, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kuroki
authors.affiliation: Respiratory Care Clinic, Nippon Medical School, 4-7-15-8F Kudan-Minami, Chiyoda-ku, Tokyo 102-0074, Japan.
authors.forename: Kozui
authors.initials: K
authors.lastname: Kida
authors.affiliation: Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center, RIKEN Global Research Cluster, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan. Electronic address: dglycotani@riken.jp.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015415:Biomarkers / Q000097:blood; D005260:Female; D005643:Fucose; D006031:Glycosylation; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood*; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood*
chemical_list: D015415:Biomarkers; D037663:Pulmonary Surfactant-Associated Protein D; D005643:Fucose
keywords: AQ-labeling; Antibody–lectin EIA; Biomarker; COPD; Core-fucose; SP-D