N-glycosylation patterns of plasma proteins and immunoglobulin G in chronic obstructive pulmonary disease

Abstract Background Chronic obstructive pulmonary disease (COPD) is a complex condition, whose diagnosis requires spirometric assessment. However, considering its heterogeneity, subjects with similar spirometric parameters do not necessarily have the same functional status. To overcome this limitati...

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Main Authors: Tamara Pavić, Dario Dilber, Domagoj Kifer, Najda Selak, Toma Keser, Đivo Ljubičić, Andrea Vukić Dugac, Gordan Lauc, Lada Rumora, Olga Gornik
Format: Article
Language:English
Published: BMC 2018-11-01
Series:Journal of Translational Medicine
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12967-018-1695-0
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author Tamara Pavić
Dario Dilber
Domagoj Kifer
Najda Selak
Toma Keser
Đivo Ljubičić
Andrea Vukić Dugac
Gordan Lauc
Lada Rumora
Olga Gornik
author_facet Tamara Pavić
Dario Dilber
Domagoj Kifer
Najda Selak
Toma Keser
Đivo Ljubičić
Andrea Vukić Dugac
Gordan Lauc
Lada Rumora
Olga Gornik
author_sort Tamara Pavić
collection DOAJ
description Abstract Background Chronic obstructive pulmonary disease (COPD) is a complex condition, whose diagnosis requires spirometric assessment. However, considering its heterogeneity, subjects with similar spirometric parameters do not necessarily have the same functional status. To overcome this limitation novel biomarkers for COPD have been investigated. Therefore, we aimed to explore the potential value of N-glycans as COPD biomarkers and to examine the individual variation of plasma protein and immunoglobulin G (IgG) glycosylation profiles in subjects with COPD and healthy controls. Methods Both the total plasma protein and IgG N-glycome have been profiled in the total of 137 patients with COPD and 95 matching controls from Croatia. Replication cohort consisted of 61 subjects with COPD and 148 controls recruited at another Croatian medical centre. Results Plasma protein N-glycome in COPD subjects exhibited significant decrease in low branched and conversely, an increase in more complex glycan structures (tetragalactosylated, trisialylated, tetrasialylated and antennary fucosylated glycoforms). We also observed a significant decline in plasma monogalactosylated species, and the same change replicated in IgG glycome. N-glycans also showed value in distinguishing subjects in different COPD GOLD stages, where the relative abundance of more complex glycan structures increased as the disease progressed. Glycans also showed statistically significant associations with the frequency of exacerbations and demonstrated to be affected by smoking, which is the major risk factor for COPD development. Conclusions This study showed that complexity of glycans associates with COPD, mirroring also the disease severity. Moreover, changes in N-glycome associate with exacerbation frequency and are affected by smoking. In general, this study provided new insights into plasma protein and IgG N-glycome changes occurring in COPD and pointed out potential novel markers of the disease progression and severity.
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spelling doaj.art-15099fa04584425fb97f780738a005962022-12-22T03:06:08ZengBMCJournal of Translational Medicine1479-58762018-11-0116111510.1186/s12967-018-1695-0N-glycosylation patterns of plasma proteins and immunoglobulin G in chronic obstructive pulmonary diseaseTamara Pavić0Dario Dilber1Domagoj Kifer2Najda Selak3Toma Keser4Đivo Ljubičić5Andrea Vukić Dugac6Gordan Lauc7Lada Rumora8Olga Gornik9Faculty of Pharmacy and Biochemistry, University of ZagrebDeparment of Cardiology, County Hospital ČakovecFaculty of Pharmacy and Biochemistry, University of ZagrebFaculty of Pharmacy and Biochemistry, University of ZagrebFaculty of Pharmacy and Biochemistry, University of ZagrebDepartment of Pulmonology, Clinical Hospital DubravaClinical Department for Lung Diseases Jordanovac, University Hospital CentreFaculty of Pharmacy and Biochemistry, University of ZagrebFaculty of Pharmacy and Biochemistry, University of ZagrebFaculty of Pharmacy and Biochemistry, University of ZagrebAbstract Background Chronic obstructive pulmonary disease (COPD) is a complex condition, whose diagnosis requires spirometric assessment. However, considering its heterogeneity, subjects with similar spirometric parameters do not necessarily have the same functional status. To overcome this limitation novel biomarkers for COPD have been investigated. Therefore, we aimed to explore the potential value of N-glycans as COPD biomarkers and to examine the individual variation of plasma protein and immunoglobulin G (IgG) glycosylation profiles in subjects with COPD and healthy controls. Methods Both the total plasma protein and IgG N-glycome have been profiled in the total of 137 patients with COPD and 95 matching controls from Croatia. Replication cohort consisted of 61 subjects with COPD and 148 controls recruited at another Croatian medical centre. Results Plasma protein N-glycome in COPD subjects exhibited significant decrease in low branched and conversely, an increase in more complex glycan structures (tetragalactosylated, trisialylated, tetrasialylated and antennary fucosylated glycoforms). We also observed a significant decline in plasma monogalactosylated species, and the same change replicated in IgG glycome. N-glycans also showed value in distinguishing subjects in different COPD GOLD stages, where the relative abundance of more complex glycan structures increased as the disease progressed. Glycans also showed statistically significant associations with the frequency of exacerbations and demonstrated to be affected by smoking, which is the major risk factor for COPD development. Conclusions This study showed that complexity of glycans associates with COPD, mirroring also the disease severity. Moreover, changes in N-glycome associate with exacerbation frequency and are affected by smoking. In general, this study provided new insights into plasma protein and IgG N-glycome changes occurring in COPD and pointed out potential novel markers of the disease progression and severity.http://link.springer.com/article/10.1186/s12967-018-1695-0N-glycosylationCOPDBiomarkersPlasma glycoproteinsImmunoglobulin G
spellingShingle Tamara Pavić
Dario Dilber
Domagoj Kifer
Najda Selak
Toma Keser
Đivo Ljubičić
Andrea Vukić Dugac
Gordan Lauc
Lada Rumora
Olga Gornik
N-glycosylation patterns of plasma proteins and immunoglobulin G in chronic obstructive pulmonary disease
Journal of Translational Medicine
N-glycosylation
COPD
Biomarkers
Plasma glycoproteins
Immunoglobulin G
title N-glycosylation patterns of plasma proteins and immunoglobulin G in chronic obstructive pulmonary disease
title_full N-glycosylation patterns of plasma proteins and immunoglobulin G in chronic obstructive pulmonary disease
title_fullStr N-glycosylation patterns of plasma proteins and immunoglobulin G in chronic obstructive pulmonary disease
title_full_unstemmed N-glycosylation patterns of plasma proteins and immunoglobulin G in chronic obstructive pulmonary disease
title_short N-glycosylation patterns of plasma proteins and immunoglobulin G in chronic obstructive pulmonary disease
title_sort n glycosylation patterns of plasma proteins and immunoglobulin g in chronic obstructive pulmonary disease
topic N-glycosylation
COPD
Biomarkers
Plasma glycoproteins
Immunoglobulin G
url http://link.springer.com/article/10.1186/s12967-018-1695-0
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