Skip to main content
Top
Published in: Journal of Translational Medicine 1/2018

Open Access 01-12-2018 | Research

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

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

Published in: Journal of Translational Medicine | Issue 1/2018

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Vestbo J, Hurd SS, Agustí AG, Jones PW, Vogelmeier C, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;187:347–65.CrossRef Vestbo J, Hurd SS, Agustí AG, Jones PW, Vogelmeier C, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;187:347–65.CrossRef
2.
go back to reference Adeloye D, Chua S, Lee C, Basquill C, Papana A, Theodoratou E, et al. Global and regional estimates of COPD prevalence: systematic review and meta-analysis. J Glob Health. 2015;5:020415.CrossRef Adeloye D, Chua S, Lee C, Basquill C, Papana A, Theodoratou E, et al. Global and regional estimates of COPD prevalence: systematic review and meta-analysis. J Glob Health. 2015;5:020415.CrossRef
3.
go back to reference Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ, editors. Global burden of disease and risk factors. Washington (DC): World Bank; 2006. Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ, editors. Global burden of disease and risk factors. Washington (DC): World Bank; 2006.
5.
go back to reference Franciosi LG, Page CP, Celli BR, Cazzola M, Walker MJ, Danhof M, et al. Markers of disease severity in chronic obstructive pulmonary disease. Pulm Pharmacol Ther. 2006;19:189–99.CrossRef Franciosi LG, Page CP, Celli BR, Cazzola M, Walker MJ, Danhof M, et al. Markers of disease severity in chronic obstructive pulmonary disease. Pulm Pharmacol Ther. 2006;19:189–99.CrossRef
6.
go back to reference Vestbo J, Anderson W, Coxson HO, Crim C, Dawber F, Edwards L, et al. Evaluation of COPD longitudinally to identify predictive surrogate end-points (ECLIPSE). Eur Respir J. 2008;31:869–73.CrossRef Vestbo J, Anderson W, Coxson HO, Crim C, Dawber F, Edwards L, et al. Evaluation of COPD longitudinally to identify predictive surrogate end-points (ECLIPSE). Eur Respir J. 2008;31:869–73.CrossRef
7.
8.
go back to reference Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. GOLD executive summary. Am J Respir Crit Care Med. 2017;195:557–82.CrossRef Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. GOLD executive summary. Am J Respir Crit Care Med. 2017;195:557–82.CrossRef
9.
go back to reference Park HY, Churg A, Wright JL, Li Y, Tam S, Man SFP, et al. Club cell protein 16 and disease progression in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;188:1413–9.CrossRef Park HY, Churg A, Wright JL, Li Y, Tam S, Man SFP, et al. Club cell protein 16 and disease progression in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;188:1413–9.CrossRef
10.
go back to reference Lomas DA, Silverman EK, Edwards LD, Locantore NW, Miller BE, Horstman DH, et al. Serum surfactant protein D is steroid sensitive and associated with exacerbations of COPD. Eur Respir J. 2009;34:95–102.CrossRef Lomas DA, Silverman EK, Edwards LD, Locantore NW, Miller BE, Horstman DH, et al. Serum surfactant protein D is steroid sensitive and associated with exacerbations of COPD. Eur Respir J. 2009;34:95–102.CrossRef
11.
go back to reference Thomsen M, Ingebrigtsen TS, Marott JL, Dahl M, Lange P, Vestbo J, et al. Inflammatory biomarkers and exacerbations in chronic obstructive pulmonary disease. JAMA. 2013;309:2353–61.CrossRef Thomsen M, Ingebrigtsen TS, Marott JL, Dahl M, Lange P, Vestbo J, et al. Inflammatory biomarkers and exacerbations in chronic obstructive pulmonary disease. JAMA. 2013;309:2353–61.CrossRef
12.
go back to reference Casaburi R, Celli B, Crapo J, Criner G, Croxton T, Gaw A, et al. The COPD biomarker qualification consortium (CBQC). COPD J Chronic Obstr Pulm Dis. 2013;10:367–77.CrossRef Casaburi R, Celli B, Crapo J, Criner G, Croxton T, Gaw A, et al. The COPD biomarker qualification consortium (CBQC). COPD J Chronic Obstr Pulm Dis. 2013;10:367–77.CrossRef
13.
go back to reference Celli BR, Locantore N, Yates J, Tal-Singer R, Miller BE, Bakke P, et al. Inflammatory biomarkers improve clinical prediction of mortality in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;185:1065–72.CrossRef Celli BR, Locantore N, Yates J, Tal-Singer R, Miller BE, Bakke P, et al. Inflammatory biomarkers improve clinical prediction of mortality in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;185:1065–72.CrossRef
14.
go back to reference Duvoix A, Dickens J, Haq I, Mannino D, Miller B, Tal-Singer R, et al. Blood fibrinogen as a biomarker of chronic obstructive pulmonary disease. Thorax. 2013;68:670–6.CrossRef Duvoix A, Dickens J, Haq I, Mannino D, Miller B, Tal-Singer R, et al. Blood fibrinogen as a biomarker of chronic obstructive pulmonary disease. Thorax. 2013;68:670–6.CrossRef
16.
go back to reference Aksu F, Çapan N, Aksu K, Ofluoğlu R, Canbakan S, Yavuz B, et al. C-reactive protein levels are raised in stable Chronic obstructive pulmonary disease patients independent of smoking behavior and biomass exposure. J Thorac Dis. 2013;5:414–21.PubMedPubMedCentral Aksu F, Çapan N, Aksu K, Ofluoğlu R, Canbakan S, Yavuz B, et al. C-reactive protein levels are raised in stable Chronic obstructive pulmonary disease patients independent of smoking behavior and biomass exposure. J Thorac Dis. 2013;5:414–21.PubMedPubMedCentral
17.
go back to reference Bozinovski S, Hutchinson A, Thompson M, MacGregor L, Black J, Giannakis E, et al. Serum amyloid a is a biomarker of acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008;177:269–78.CrossRef Bozinovski S, Hutchinson A, Thompson M, MacGregor L, Black J, Giannakis E, et al. Serum amyloid a is a biomarker of acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008;177:269–78.CrossRef
18.
go back to reference Agustí A, Edwards LD, Rennard SI, MacNee W, Tal-Singer R, Miller BE, et al. Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype. PLoS ONE. 2012;7:e37483.CrossRef Agustí A, Edwards LD, Rennard SI, MacNee W, Tal-Singer R, Miller BE, et al. Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype. PLoS ONE. 2012;7:e37483.CrossRef
19.
go back to reference Ohtsubo K, Marth JD. Glycosylation in cellular mechanisms of health and disease. Cell. 2006;126:855–67.CrossRef Ohtsubo K, Marth JD. Glycosylation in cellular mechanisms of health and disease. Cell. 2006;126:855–67.CrossRef
20.
go back to reference Gornik O, Pavić T, Lauc G. Alternative glycosylation modulates function of IgG and other proteins—implications on evolution and disease. Biochim Biophys Acta. 2012;1820:1318–26.CrossRef Gornik O, Pavić T, Lauc G. Alternative glycosylation modulates function of IgG and other proteins—implications on evolution and disease. Biochim Biophys Acta. 2012;1820:1318–26.CrossRef
21.
go back to reference Novokmet M, Lukić E, Vučković F, Ðurić Ž, Keser T, Rajšl K, et al. Changes in IgG and total plasma protein glycomes in acute systemic inflammation. Sci Rep. 2014;4:4347.CrossRef Novokmet M, Lukić E, Vučković F, Ðurić Ž, Keser T, Rajšl K, et al. Changes in IgG and total plasma protein glycomes in acute systemic inflammation. Sci Rep. 2014;4:4347.CrossRef
22.
go back to reference An HJ, Kronewitter SR, de Leoz MLA, Lebrilla CB. Glycomics and disease markers. Curr Opin Chem Biol. 2009;13:601–7.CrossRef An HJ, Kronewitter SR, de Leoz MLA, Lebrilla CB. Glycomics and disease markers. Curr Opin Chem Biol. 2009;13:601–7.CrossRef
23.
go back to reference Anthony RM, Nimmerjahn F. The role of differential Igg glycosylation in the interaction of antibodies with Fcγrs in vivo. Curr Opin Organ Transpl. 2011;16:7–14.CrossRef Anthony RM, Nimmerjahn F. The role of differential Igg glycosylation in the interaction of antibodies with Fcγrs in vivo. Curr Opin Organ Transpl. 2011;16:7–14.CrossRef
25.
go back to reference Campbell MP, Royle L, Radcliffe CM, Dwek RA, Rudd PM. GlycoBase and autoGU: tools for HPLC-based glycan analysis. Bioinformatics. 2008;24:1214–6.CrossRef Campbell MP, Royle L, Radcliffe CM, Dwek RA, Rudd PM. GlycoBase and autoGU: tools for HPLC-based glycan analysis. Bioinformatics. 2008;24:1214–6.CrossRef
26.
go back to reference Abrahams JL, Campbell MP, Packer NH. Building a PGC-LC-MS N-glycan retention library and elution mapping resource. Glycoconj J. 2018;35:15–29.CrossRef Abrahams JL, Campbell MP, Packer NH. Building a PGC-LC-MS N-glycan retention library and elution mapping resource. Glycoconj J. 2018;35:15–29.CrossRef
27.
go back to reference Keser T, Gornik I, Vučković F, Selak N, Pavić T, Lukić E, et al. Increased plasma N-glycome complexity is associated with higher risk of type 2 diabetes. Diabetologia. 2017;60:2352–60.CrossRef Keser T, Gornik I, Vučković F, Selak N, Pavić T, Lukić E, et al. Increased plasma N-glycome complexity is associated with higher risk of type 2 diabetes. Diabetologia. 2017;60:2352–60.CrossRef
28.
go back to reference Trbojević-Akmačić I, Vučković F, Vilaj M, Skelin A, Karssen LC, Krištić J, et al. Plasma N-glycome composition associates with chronic low back pain. Biochim Biophys Acta. 2018;1862:2124–33.CrossRef Trbojević-Akmačić I, Vučković F, Vilaj M, Skelin A, Karssen LC, Krištić J, et al. Plasma N-glycome composition associates with chronic low back pain. Biochim Biophys Acta. 2018;1862:2124–33.CrossRef
29.
go back to reference Lowe JB. Glycosylation in the control of selectin counter-receptor structure and function. Immunol Rev. 2002;186:19–36.CrossRef Lowe JB. Glycosylation in the control of selectin counter-receptor structure and function. Immunol Rev. 2002;186:19–36.CrossRef
30.
go back to reference Sperandio M. Selectins and glycosyltransferases in leukocyte rolling in vivo. FEBS J. 2006;273:4377–89.CrossRef Sperandio M. Selectins and glycosyltransferases in leukocyte rolling in vivo. FEBS J. 2006;273:4377–89.CrossRef
31.
go back to reference Malhotra R, Wormald MR, Rudd PM, Fischer PB, Dwek RA, Sim RB. Glycosylation changes of IgG associated with rheumatoid arthritis can activate complement via the mannose-binding protein. Nat Med. 1995;1:237–43.CrossRef Malhotra R, Wormald MR, Rudd PM, Fischer PB, Dwek RA, Sim RB. Glycosylation changes of IgG associated with rheumatoid arthritis can activate complement via the mannose-binding protein. Nat Med. 1995;1:237–43.CrossRef
32.
go back to reference Gornik O, Lauc G. Glycosylation of serum proteins in inflammatory diseases. Dis Markers. 2008;25:267–78.CrossRef Gornik O, Lauc G. Glycosylation of serum proteins in inflammatory diseases. Dis Markers. 2008;25:267–78.CrossRef
33.
go back to reference Vučković F, Krištić J, Gudelj I, Teruel M, Keser T, Pezer M, et al. Association of systemic lupus erythematosus with decreased immunosuppressive potential of the IgG glycome. Arthritis Rheumatol. 2015;67:2978–89.CrossRef Vučković F, Krištić J, Gudelj I, Teruel M, Keser T, Pezer M, et al. Association of systemic lupus erythematosus with decreased immunosuppressive potential of the IgG glycome. Arthritis Rheumatol. 2015;67:2978–89.CrossRef
34.
go back to reference Feghali-Bostwick CA, Gadgil AS, Otterbein LE, Pilewski JM, Stoner MW, Csizmadia E, et al. Autoantibodies in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008;177:156–63.CrossRef Feghali-Bostwick CA, Gadgil AS, Otterbein LE, Pilewski JM, Stoner MW, Csizmadia E, et al. Autoantibodies in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008;177:156–63.CrossRef
35.
go back to reference Celli BR, Barnes PJ. Exacerbations of chronic obstructive pulmonary disease. Eur Respir J. 2007;29:1224–38.CrossRef Celli BR, Barnes PJ. Exacerbations of chronic obstructive pulmonary disease. Eur Respir J. 2007;29:1224–38.CrossRef
36.
go back to reference Hurst JR, Perera WR, Wilkinson TMA, Donaldson GC, Wedzicha JA. Systemic and upper and lower airway inflammation at exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2006;173:71–8.CrossRef Hurst JR, Perera WR, Wilkinson TMA, Donaldson GC, Wedzicha JA. Systemic and upper and lower airway inflammation at exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2006;173:71–8.CrossRef
37.
go back to reference Anderson HR, Spix C, Medina S, Schouten JP, Castellsague J, Rossi G, et al. Air pollution and daily admissions for chronic obstructive pulmonary disease in 6 European cities: results from the APHEA project. Eur Respir J. 1997;10:1064–71.CrossRef Anderson HR, Spix C, Medina S, Schouten JP, Castellsague J, Rossi G, et al. Air pollution and daily admissions for chronic obstructive pulmonary disease in 6 European cities: results from the APHEA project. Eur Respir J. 1997;10:1064–71.CrossRef
38.
go back to reference Leitao Filho FS, Ra SW, Mattman A, Schellenberg RS, Criner GJ, Woodruff PG, et al. Serum IgG subclass levels and risk of exacerbations and hospitalizations in patients with COPD. Respir Res. 2018;19:30.CrossRef Leitao Filho FS, Ra SW, Mattman A, Schellenberg RS, Criner GJ, Woodruff PG, et al. Serum IgG subclass levels and risk of exacerbations and hospitalizations in patients with COPD. Respir Res. 2018;19:30.CrossRef
39.
go back to reference Knežević A, Gornik O, Polašek O, Pučić M, Redžić I, Novokmet M, et al. Effects of aging, body mass index, plasma lipid profiles, and smoking on human plasma N-glycans. Glycobiology. 2010;20:959–69.CrossRef Knežević A, Gornik O, Polašek O, Pučić M, Redžić I, Novokmet M, et al. Effects of aging, body mass index, plasma lipid profiles, and smoking on human plasma N-glycans. Glycobiology. 2010;20:959–69.CrossRef
40.
go back to reference Vasseur JA, Goetz JA, Alley WR, Novotny MV. Smoking and lung cancer-induced changes in N-glycosylation of blood serum proteins. Glycobiology. 2012;22:1684–708.CrossRef Vasseur JA, Goetz JA, Alley WR, Novotny MV. Smoking and lung cancer-induced changes in N-glycosylation of blood serum proteins. Glycobiology. 2012;22:1684–708.CrossRef
41.
go back to reference Wahl A, Kasela S, Carnero-Montoro E, van Iterson M, Štambuk J, Sharma S, et al. IgG glycosylation and DNA methylation are interconnected with smoking. Biochim Biophys Acta Gen Subj. 2018;1862:637–48.CrossRef Wahl A, Kasela S, Carnero-Montoro E, van Iterson M, Štambuk J, Sharma S, et al. IgG glycosylation and DNA methylation are interconnected with smoking. Biochim Biophys Acta Gen Subj. 2018;1862:637–48.CrossRef
42.
go back to reference Iida S, Kuni-Kamochi R, Mori K, Misaka H, Inoue M, Okazaki A, et al. Two mechanisms of the enhanced antibody-dependent cellular cytotoxicity (ADCC) efficacy of non-fucosylated therapeutic antibodies in human blood. BMC Cancer. 2009;9:58.CrossRef Iida S, Kuni-Kamochi R, Mori K, Misaka H, Inoue M, Okazaki A, et al. Two mechanisms of the enhanced antibody-dependent cellular cytotoxicity (ADCC) efficacy of non-fucosylated therapeutic antibodies in human blood. BMC Cancer. 2009;9:58.CrossRef
43.
go back to reference Davies J, Jiang L, Pan LZ, LaBarre MJ, Anderson D, Reff M. Expression of GnTIII in a recombinant anti-CD20 CHO production cell line: expression of antibodies with altered glycoforms leads to an increase in ADCC through higher affinity for FC gamma RIII. Biotechnol Bioeng. 2001;74:288–94.CrossRef Davies J, Jiang L, Pan LZ, LaBarre MJ, Anderson D, Reff M. Expression of GnTIII in a recombinant anti-CD20 CHO production cell line: expression of antibodies with altered glycoforms leads to an increase in ADCC through higher affinity for FC gamma RIII. Biotechnol Bioeng. 2001;74:288–94.CrossRef
44.
go back to reference Lee J, Taneja V, Vassallo R. Cigarette smoking and inflammation. J Dent Res. 2012;91:142–9.CrossRef Lee J, Taneja V, Vassallo R. Cigarette smoking and inflammation. J Dent Res. 2012;91:142–9.CrossRef
45.
go back to reference van der Vaart H, Postma DS, Timens W, Hacken NHTT. Acute effects of cigarette smoke on inflammation and oxidative stress: a review. Thorax. 2004;59:713–21.CrossRef van der Vaart H, Postma DS, Timens W, Hacken NHTT. Acute effects of cigarette smoke on inflammation and oxidative stress: a review. Thorax. 2004;59:713–21.CrossRef
Metadata
Title
N-glycosylation patterns of plasma proteins and immunoglobulin G in chronic obstructive pulmonary disease
Authors
Tamara Pavić
Dario Dilber
Domagoj Kifer
Najda Selak
Toma Keser
Đivo Ljubičić
Andrea Vukić Dugac
Gordan Lauc
Lada Rumora
Olga Gornik
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2018
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-018-1695-0

Other articles of this Issue 1/2018

Journal of Translational Medicine 1/2018 Go to the issue