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.

BIOLOGICAL SIGNIFICANCE:

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: Emi Ito, Ritsuko Oka, Takeo Ishii, Hiroaki Korekane, Ayako Kurimoto, Yasuhiko Kizuka, Shinobu Kitazume, Shigeru Ariki, Motoko Takahashi, Yoshio Kuroki, Kozui Kida, Naoyuki Taniguchi
• Journal: Journal of proteomics (J Proteomics) Vol. 127 Issue Pt B Pg. 386-94 (Sep 08 2015) ISSN: 1876-7737 [Electronic] Netherlands
• PMID: 26206179 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Biomarkers
• Pulmonary Surfactant-Associated Protein D
• Fucose

Topics

• Aged
• Aged, 80 and over
• Animals
• Biomarkers (blood)
• Female
• Fucose
• Glycosylation
• Humans
• Male
• Mice
• Mice, Knockout
• Middle Aged
• Pulmonary Disease, Chronic Obstructive (blood)
• Pulmonary Surfactant-Associated Protein D (blood)