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

Tamara Pavić,Đivo Ljubičić,Lada Rumora,Dario Dilber,Najda Selak,Toma Keser,Olga Gornik,Domagoj Kifer,Andrea Vukić Dugac,Gordan Lauc

doi:10.1186/s12967-018-1695-0

Abstract

BackgroundChronic 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.MethodsBoth 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.ResultsPlasma 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.ConclusionsThis 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.

Highlights

Chronic obstructive pulmonary disease (COPD) is a complex condition, whose diagnosis requires spirometric assessment
Replication cohort consisted of 61 subjects with COPD and 148 controls recruited at another medical centre
Based on the similar structural features of the analysed glycans, 16 additional derived glycan traits were calculated for plasma protein glycome and nine derived glycan traits were calculated for immunoglobulin G (IgG) glycome (Table 1)

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is a complex condition, whose diagnosis requires spirometric assessment. 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. Considering COPD heterogeneity, patients with similar FEV1 do not necessarily have the same functional status or underlying pathology, making spirometric assessment alone insufficient for thorough characterization of the individual’s status [6]. There was a substantial necessity for measures/biomarkers which would enable reliable patient assessment, management of the treatment and monitoring of the disease progression over shorter periods of time

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