Advertisement

IgG Glycans as a Biomarker of Biological Age

  • M. Vilaj
  • I. Gudelj
  • I. Trbojević-Akmačić
  • G. Lauc
  • M. PezerEmail author
Chapter
Part of the Healthy Ageing and Longevity book series (HAL, volume 10)

Abstract

Immunoglobulin G (IgG) has an important role in various processes of the immune response and its functions can be modulated by N-glycans attached to its Fab and Fc portions. The composition of IgG glycans can be deciphered using different analytical methods, based on liquid chromatography, mass spectrometry and capillary electrophoresis. IgG glycome composition is partly heritable, but is also under the influence of various environmental factors. It therefore represents an interface between genes and environment, as evidenced by IgG glycosylation pattern changes associated with chronological age, various diseases and lifestyle-related variables. IgG glycans are therefore considered an excellent biomarker of the general health state of a person, i.e. biological age.

Keywords

IgG glycome Aging Diseases Biological age Biomarker Inflammaging 

Abbreviations

ADCC

Antibody-dependent cellular cytotoxicity

CGE-LIF

Capillary gel electrophoresis with laser induced fluorescence detection

CH

Constant heavy domain

CL

Constant light domain

Fab

Fragment antigen binding

Fc

Fragment crystallizable

FcγR

Fcγ receptor

IgG

Immunoglobulin G

IVIg

Intravenous immunoglobulin

LC-ESI-MS

Liquid chromatography electrospray ionization mass spectrometry

MALDI-TOF-MS

Matrix assisted laser desorption/ionization time-of-flight mass spectrometry

RA

Rheumatoid arthritis

TPNG

Total plasma N-glycome

UHPLC-FLR

Ultra-high-performance liquid chromatography with fluorescence detection

VL

Variable light domain

VH

Variable heavy domain

References

  1. Alavi A, Arden N, Spector TD, Axford JS (2000) Immunoglobulin G glycosylation and clinical outcome in rheumatoid arthritis during pregnancy. J Rheumatol 27:1379–1385PubMedGoogle Scholar
  2. Albert H, Collin M, Dudziak D et al (2008) In vivo enzymatic modulation of IgG glycosylation inhibits autoimmune disease in an IgG subclass-dependent manner. Proc Natl Acad Sci U.S.A 105:15005–15009.  https://doi.org/10.1073/pnas.0808248105CrossRefPubMedPubMedCentralGoogle Scholar
  3. Anthony RM, Nimmerjahn F (2011) The role of differential IgG glycosylation in the interaction of antibodies with FcγRs in vivo. Curr Opin Organ Transplant 16:7–14.  https://doi.org/10.1097/MOT.0b013e328342538fCrossRefPubMedGoogle Scholar
  4. Anumula KR (2012) Quantitative glycan profiling of normal human plasma derived immunoglobulin and its fragments Fab and Fc. J Immunol Methods 382:167–176.  https://doi.org/10.1016/j.jim.2012.05.022CrossRefPubMedGoogle Scholar
  5. Arai Y, Martin-Ruiz CM, Takayama M et al (2015) Inflammation, but not telomere length, predicts successful ageing at extreme old age: a longitudinal study of semi-supercentenarians. EBioMedicine 2:1549–1558.  https://doi.org/10.1016/j.ebiom.2015.07.029CrossRefPubMedPubMedCentralGoogle Scholar
  6. Arnold JN, Wormald MR (2007) The impact of glycosylation on the biological function and structure of human immunoglobulins. Annu Rev Immunol 25:21–50.  https://doi.org/10.1146/annurev.immunol.25.022106.141702CrossRefPubMedGoogle Scholar
  7. Arnold JN, Dwek RA, Rudd PM, Sim RB (2006) Mannan binding lectin and its interaction with immunoglobulins in health and in disease. Immunol Lett 106:103–110CrossRefGoogle Scholar
  8. Arnold JN, Wormald MR, Sim RB et al (2007) The impact of glycosylation on the biological function and structure of human immunoglobulins. Annu Rev Immunol 25:21–50.  https://doi.org/10.1146/annurev.immunol.25.022106.141702CrossRefPubMedGoogle Scholar
  9. Baković MP, Selman MHJ, Hoffmann M et al (2013) High-throughput IgG Fc N-glycosylation profiling by mass spectrometry of glycopeptides. J Proteome Res 12:821–831.  https://doi.org/10.1021/pr300887zCrossRefPubMedGoogle Scholar
  10. Banda NK, Wood AK, Takahashi K et al (2008) Initiation of the alternative pathway of murine complement by immune complexes is dependent on N-glycans in IgG antibodies. Arthritis Rheum 58:3081–3089.  https://doi.org/10.1002/art.23865CrossRefPubMedPubMedCentralGoogle Scholar
  11. Böhm S, Schwab I, Lux A, Nimmerjahn F (2012) The role of sialic acid as a modulator of the anti-inflammatory activity of IgG. Semin Immunopathol 34:443–453.  https://doi.org/10.1007/s00281-012-0308-xCrossRefPubMedGoogle Scholar
  12. Bondt A, Selman MHJ, Deelder AM et al (2013) Association between galactosylation of immunoglobulin G and improvement of rheumatoid arthritis during pregnancy is independent of sialylation. J Proteome Res 12:4522–4531.  https://doi.org/10.1021/pr400589mCrossRefPubMedGoogle Scholar
  13. Bondt A, Rombouts Y, Selman MHJ et al (2014) Immunoglobulin G (IgG) Fab glycosylation analysis using a new mass spectrometric high-throughput profiling method reveals pregnancy-associated changes. Mol Cell Proteomics 13:3029–3039.  https://doi.org/10.1074/mcp.M114.039537CrossRefPubMedPubMedCentralGoogle Scholar
  14. Bones J, Mittermayr S, O’Donoghue N et al (2010) Ultra performance liquid chromatographic profiling of serum N-glycans for fast and efficient identification of cancer associated alterations in glycosylation. Anal Chem 82:10208–10215.  https://doi.org/10.1021/ac102860wCrossRefPubMedGoogle Scholar
  15. Bunz SC, Rapp E, Neusüss C (2013) Capillary electrophoresis/mass spectrometry of APTS-labeled glycans for the identification of unknown glycan species in capillary electrophoresis/laser- induced fluorescence systems. Anal Chem 85:10218–10224.  https://doi.org/10.1021/ac401930jCrossRefPubMedGoogle Scholar
  16. Clerc F, Reiding KR, Jansen BC, et al (2015) Human plasma protein N-glycosylation. Glycoconj J 1–35.  https://doi.org/10.1007/s10719-015-9626-2CrossRefGoogle Scholar
  17. Coloma MJ, Trinh RK, Martinez AR, Morrison SL (1999) Position effects of variable region carbohydrate on the affinity and in vivo behavior of an anti-(1→6) dextran antibody. J Immunol 162:2162–2170PubMedGoogle Scholar
  18. Croce A, Firuzi O, Altieri F et al (2007) Effect of infliximab on the glycosylation of IgG of patients with rheumatoid arthritis. J Clin Lab Anal 21:303–314.  https://doi.org/10.1002/jcla.20191CrossRefPubMedGoogle Scholar
  19. Cymer F, Beck H, Rohde A, Reusch D (2018) Therapeutic monoclonal antibody N-glycosylation—Structure, function and therapeutic potential. Biologicals 52:1–11.  https://doi.org/10.1016/j.biologicals.2017.11.001CrossRefPubMedGoogle Scholar
  20. Dall’Olio F, Vanhooren V, Chen CC et al (2013) N-glycomic biomarkers of biological aging and longevity: a link with inflammaging. Ageing Res. Rev. 12:685–698CrossRefGoogle Scholar
  21. Dalziel M, McFarlane I, Axford JS (1999) Lectin analysis of human immunoglobulin G N-glycan sialylation. Glycoconj J 16:801–807.  https://doi.org/10.1023/A:1007183915921CrossRefPubMedGoogle Scholar
  22. De Haan N, Reiding KR, Driessen G et al (2016) Changes in healthy human IgG Fc-glycosylation after birth and during early childhood. J Proteome Res 15:1853–1861.  https://doi.org/10.1021/acs.jproteome.6b00038CrossRefPubMedGoogle Scholar
  23. De Martinis M, Franceschi C, Monti D, Ginaldi L (2005) Inflamm-ageing and lifelong antigenic load as major determinants of ageing rate and longevity. FEBS Lett 579:2035–2039CrossRefGoogle Scholar
  24. Dekkers G, Treffers L, Plomp R, et al (2017) Decoding the human immunoglobulin G-glycan repertoire reveals a spectrum of Fc-receptor- and complement-mediated-effector activities. Front Immunol 8.  https://doi.org/10.3389/fimmu.2017.00877
  25. Dell A (2001) Glycoprotein structure determination by mass spectrometry. Science 80(291):2351–2356.  https://doi.org/10.1126/science.1058890CrossRefGoogle Scholar
  26. Desantos-Garcia JL, Khalil SI, Hussein A et al (2011) Enhanced sensitivity of LC-MS analysis of permethylated N-glycans through online purification. Electrophoresis 32:3516–3525.  https://doi.org/10.1002/elps.201100378CrossRefPubMedPubMedCentralGoogle Scholar
  27. Dong X, Storkus WJ, Salter RD (1999) Binding and uptake of agalactosyl IgG by mannose receptor on macrophages and dendritic cells. J Immunol 163:5427–5434PubMedGoogle Scholar
  28. Dunn-Walters D, Boursier L, Spencer J (2000) Effect of somatic hypermutation on potential N-glycosylation sites in human immunoglobulin heavy chain variable regions. Mol Immunol 37:107–113CrossRefGoogle Scholar
  29. Endo T, Iwakura Y, Kobata A (1993) Structural changes in the N-linked sugar chains of serum immunoglobulin G of HTLV-I transgenic mice. Biochem Biophys Res Commun 192:1004–1010CrossRefGoogle Scholar
  30. Ferrara C, Grau S, Jager C et al (2011) Unique carbohydrate-carbohydrate interactions are required for high affinity binding between Fc RIII and antibodies lacking core fucose. Proc Natl Acad Sci 108:12669–12674.  https://doi.org/10.1073/pnas.1108455108CrossRefPubMedGoogle Scholar
  31. Flögel M, Lauc G, Gornik I, Maček B (1998) Fucosylation and galactosylation of IgG heavy chains differ between acute and remission phases of juvenile chronic arthritis. Clin Chem Lab Med 36:99–102.  https://doi.org/10.1515/CCLM.1998.018CrossRefPubMedGoogle Scholar
  32. Franceschi C (2007) Inflammaging as a major characteristic of old people: can it be prevented or cured? Nutr Rev 65.  https://doi.org/10.1111/j.1753-4887.2007.tb00358.xCrossRefGoogle Scholar
  33. Franceschi C, Bonafè M, Valensin S et al (2006) Inflamm-aging: an evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254.  https://doi.org/10.1111/j.1749-6632.2000.tb06651.xCrossRefGoogle Scholar
  34. Franceschi C, Capri M, Monti D et al (2007) Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 128:92–105.  https://doi.org/10.1016/j.mad.2006.11.016CrossRefGoogle Scholar
  35. Gonzalez-Quintela A, Alende R, Gude F et al (2008) Serum levels of immunoglobulins (IgG, IgA, IgM) in a general adult population and their relationship with alcohol consumption, smoking and common metabolic abnormalities. Clin Exp Immunol 151:42–50.  https://doi.org/10.1111/j.1365-2249.2007.03545.xCrossRefPubMedPubMedCentralGoogle Scholar
  36. Gornik O, Pavić T, Lauc G (2012) Alternative glycosylation modulates function of IgG and other proteins—Implications on evolution and disease. Biochim Biophys Acta Gen Subj 1820:1318–1326CrossRefGoogle Scholar
  37. Gudelj I, Lauc G, Pezer M (2018) Immunoglobulin G glycosylation in aging and diseases. Cell Immunol.  https://doi.org/10.1016/j.cellimm.2018.07.009CrossRefGoogle Scholar
  38. Hart GW, Copeland RJ (2010) Glycomics hits the big time. Cell 143:672–676.  https://doi.org/10.1016/j.cell.2010.11.008CrossRefPubMedPubMedCentralGoogle Scholar
  39. Harvey DJ (1999) Matrix-assisted laser desorption/ionization mass spectrometry of carbohydrates. Mass Spectrom Rev 18:349–450.  https://doi.org/10.1002/(SICI)1098-2787(1999)18:6%3c349:AID-MAS1%3e3.0.CO;2-HCrossRefPubMedGoogle Scholar
  40. Hebert DN, Garman SC, Molinari M (2005) The glycan code of the endoplasmic reticulum: asparagine-linked carbohydrates as protein maturation and quality-control tags. Trends Cell Biol 15:364–370CrossRefGoogle Scholar
  41. Holland M, Yagi H, Takahashi N et al (2006) Differential glycosylation of polyclonal IgG, IgG-Fc and IgG-Fab isolated from the sera of patients with ANCA-associated systemic vasculitis. Biochim Biophys Acta—Gen Subj 1760:669–677.  https://doi.org/10.1016/j.bbagen.2005.11.021CrossRefGoogle Scholar
  42. Huffman JE, Pučić-Baković M, Klarić L et al (2014) Comparative performance of four methods for high-throughput glycosylation analysis of immunoglobulin G in genetic and epidemiological research. Mol Cell Proteomics 13:1598–1610.  https://doi.org/10.1074/mcp.M113.037465CrossRefPubMedPubMedCentralGoogle Scholar
  43. Huhn C, Selman MHJ, Ruhaak LR et al (2009) IgG glycosylation analysis. Proteomics 9:882–913CrossRefGoogle Scholar
  44. Ishino T, Wang M, Mosyak L et al (2013) Engineering a monomeric Fc domain modality by N-glycosylation for the half-life extension of biotherapeutics. J Biol Chem 288:16529–16537.  https://doi.org/10.1074/jbc.M113.457689CrossRefPubMedPubMedCentralGoogle Scholar
  45. Jefferis R (2005) Glycosylation of recombinant antibody therapeutics. Biotechnol Prog 21:11–16CrossRefGoogle Scholar
  46. Ji H, Ohmura K, Mahmood U et al (2002) Arthritis critically dependent on innate immune system players. Immunity 16:157–168.  https://doi.org/10.1016/S1074-7613(02)00275-3CrossRefPubMedGoogle Scholar
  47. Kammeijer GSM, Jansen BC, Kohler I et al (2017) Sialic acid linkage differentiation of glycopeptides using capillary electrophoresis—electrospray ionization—mass spectrometry. Sci Rep 7:3733.  https://doi.org/10.1038/s41598-017-03838-yCrossRefPubMedPubMedCentralGoogle Scholar
  48. Kao D, Danzer H, Collin M et al (2015) A monosaccharide residue is sufficient to maintain mouse and human IgG subclass activity and directs IgG effector functions to cellular Fc receptors. Cell Rep 13:2376–2385.  https://doi.org/10.1016/j.celrep.2015.11.027CrossRefPubMedGoogle Scholar
  49. Kapur R, Kustiawan I, Vestrheim A et al (2014a) A prominent lack of IgG1-Fc fucosylation of platelet alloantibodies in pregnancy. Blood 123:471–480.  https://doi.org/10.1182/blood-2013-09-527978CrossRefPubMedPubMedCentralGoogle Scholar
  50. Kapur R, Della Valle L, Sonneveld M et al (2014b) Low anti-RhD IgG-Fc-fucosylation in pregnancy: a new variable predicting severity in haemolytic disease of the fetus and newborn. Br J Haematol 166:936–945.  https://doi.org/10.1111/bjh.12965CrossRefPubMedPubMedCentralGoogle Scholar
  51. Karsten CM, Pandey MK, Figge J et al (2012) Anti-inflammatory activity of IgG1 mediated by Fc galactosylation and association of FcgammaRIIB and dectin-1. Nat Med 18:1401–1406.  https://doi.org/10.1038/nm.2862CrossRefPubMedPubMedCentralGoogle Scholar
  52. Klasić M, Markulin D, Vojta A et al (2018) Promoter methylation of the MGAT3 and BACH2 genes correlates with the composition of the immunoglobulin G glycome in inflammatory bowel disease. Clin Epigenetics 10:75.  https://doi.org/10.1186/s13148-018-0507-yCrossRefPubMedPubMedCentralGoogle Scholar
  53. Knežević A, Polašek O, Gornik O et al (2009) Variability, heritability and environmental determinants of human plasma n-glycome. J Proteome Res 8:694–701.  https://doi.org/10.1021/pr800737uCrossRefPubMedGoogle Scholar
  54. Knežević A, Gornik O, Polašek O et al (2010) Effects of aging, body mass index, plasma lipid profiles, and smoking on human plasma N-glycans. Glycobiology 20:959–969.  https://doi.org/10.1093/glycob/cwq051CrossRefPubMedGoogle Scholar
  55. Komatsu E, Buist M, Roy R et al (2016) Characterization of immunoglobulins through analysis of N-glycopeptides by MALDI-TOF MS. Methods 104:170–181.  https://doi.org/10.1016/j.ymeth.2016.01.005CrossRefPubMedGoogle Scholar
  56. Krapp S, Mimura Y, Jefferis R et al (2003) Structural analysis of human IgG-Fc glycoforms reveals a correlation between glycosylation and structural integrity. J Mol Biol 325:979–989.  https://doi.org/10.1016/S0022-2836(02)01250-0CrossRefPubMedGoogle Scholar
  57. Krištić J, Vučković F, Menni C et al (2014) Glycans are a novel biomarker of chronological and biological ages. J Gerontol Ser A Biol Sci Med Sci 69:779–789.  https://doi.org/10.1093/gerona/glt190CrossRefGoogle Scholar
  58. Kumpel BM, Rademacher TW, Rook GA et al (1994) Galactosylation of human IgG monoclonal anti-D produced by EBV- transformed B-lymphoblastoid cell lines is dependent on culture method and affects Fc receptor-mediated functional activity. Hum Antibodies Hybridomas 5:143–151PubMedGoogle Scholar
  59. Kuroda Y, Nakata M, Hirose S et al (2001) Abnormal IgG galactosylation in MRL-lpr/lpr mice: pathogenic role in the development of arthritis. Pathol Int 51:909–915.  https://doi.org/10.1046/j.1440-1827.2001.01306.xCrossRefPubMedGoogle Scholar
  60. Le NPL, Bowden TA, Struwe WB, Crispin M (2016) Immune recruitment or suppression by glycan engineering of endogenous and therapeutic antibodies. Biochim Biophys Acta Gen Subj 1860:1655–1668.  https://doi.org/10.1016/j.bbagen.2016.04.016CrossRefGoogle Scholar
  61. Leader KA, Lastra GC, Kirwan JR, Elson CJ (1996) Agalactosyl IgG in aggregates from the rheumatoid joint. Br J Rheumatol 35:335–341CrossRefGoogle Scholar
  62. Leibiger H, Stner DW, Stigler R-D, Marx U (1999) Variable domain-linked oligosaccharides of a human monoclonal IgG : structure and influence on antigen binding. Biochem J 338:529–538.  https://doi.org/10.1042/0264-6021:3380529CrossRefPubMedPubMedCentralGoogle Scholar
  63. Lemmers RFH, Vilaj M, Urda D et al (2017) IgG glycan patterns are associated with type 2 diabetes in independent European populations. Biochim Biophys Acta 1861:2240–2249.  https://doi.org/10.1016/j.bbagen.2017.06.020CrossRefGoogle Scholar
  64. Malhotra R, Wormald MR, Rudd PM et al (1995) Glycosylation changes of IgG associated with rheumatooid arthritis can activate complement via the mannose-binding protein. Nat Med 1:237–243.  https://doi.org/10.1038/nm0395-237CrossRefPubMedGoogle Scholar
  65. Masuda K, Kubota T, Kaneko E et al (2007) Enhanced binding affinity for FcgammaRIIIa of fucose-negative antibody is sufficient to induce maximal antibody-dependent cellular cytotoxicity. Mol Immunol 44:3122–3131.  https://doi.org/10.1016/j.molimm.2007.02.005CrossRefPubMedGoogle Scholar
  66. Maverakis E, Kim K, Shimoda M et al (2015) Glycans in the immune system and the altered glycan theory of autoimmunity: a critical review. J Autoimmun 57:1–13.  https://doi.org/10.1016/j.jaut.2014.12.002CrossRefPubMedGoogle Scholar
  67. Menni C, Keser T, Mangino M, et al (2013) Glycosylation of immunoglobulin G: role of genetic and epigenetic influences. PLoS One 8.  https://doi.org/10.1371/journal.pone.0082558CrossRefGoogle Scholar
  68. Menni C, Gudelj I, Macdonald-Dunlop E et al (2018) Glycosylation profile of immunoglobulin G is cross-sectionally associated with cardiovascular disease risk score and subclinical atherosclerosis in two independent CohortsNovelty and significance. Circ Res 122:1555–1564.  https://doi.org/10.1161/CIRCRESAHA.117.312174CrossRefPubMedPubMedCentralGoogle Scholar
  69. Mimura Y, Church S, Ghirlando R et al (2001a) The influence of glycosylation on the thermal stability and effector function expression of human IgG1-Fc: properties of a series of truncated glycoforms. Mol Immunol 37:697–706.  https://doi.org/10.1016/S0161-5890(00)00105-XCrossRefGoogle Scholar
  70. Mimura Y, Sondermann P, Ghirlando R et al (2001b) Role of oligosaccharide residues of IgG1-Fc in FcγRIIb binding. J Biol Chem 276:45539–45547.  https://doi.org/10.1074/jbc.M107478200CrossRefPubMedGoogle Scholar
  71. Mittermayr S, Bones J, Doherty M et al (2011) Multiplexed analytical glycomics: rapid and confident IgG N-glycan structural elucidation. J Proteome Res 10:3820–3829.  https://doi.org/10.1021/pr200371sCrossRefPubMedGoogle Scholar
  72. Morelle W, Michalski J-C (2007) Analysis of protein glycosylation by mass spectrometry. Nat Protoc 2:1585–1602.  https://doi.org/10.1038/nprot.2007.227CrossRefPubMedGoogle Scholar
  73. Murphy KM (2011) Janeway’s immunobiology, 8th edn. Garland Science, New YorkGoogle Scholar
  74. Nakajima S, Iijima H, Shinzaki S et al (2011) Functional analysis of agalactosyl IgG in inflammatory bowel disease patients. Inflamm Bowel Dis 17:927–936.  https://doi.org/10.1002/ibd.21459CrossRefPubMedGoogle Scholar
  75. Nimmerjahn F, Ravetch JV (2008a) Anti-inflammatory actions of intravenous immunoglobulin. Annu Rev Immunol 26:513–533.  https://doi.org/10.1146/annurev.immunol.26.021607.090232CrossRefPubMedGoogle Scholar
  76. Nimmerjahn F, Ravetch JV (2008b) Fcγ receptors as regulators of immune responses. Nat Rev Immunol 8:34–47CrossRefGoogle Scholar
  77. Nimmerjahn F, Anthony RM, Ravetch JV (2007) Agalactosylated IgG antibodies depend on cellular Fc receptors for in vivo activity. Proc Natl Acad Sci 104:8433–8437.  https://doi.org/10.1073/pnas.0702936104CrossRefPubMedGoogle Scholar
  78. Nose M, Wigzell H (1983) Biological significance of carbohydrate chains on monoclonal antibodies. Proc Natl Acad Sci U S A 80:6632–6636.  https://doi.org/10.1073/pnas.80.21.6632CrossRefPubMedPubMedCentralGoogle Scholar
  79. Novokmet M, Lukić E, Vučković F, et al (2014) Changes in IgG and total plasma protein glycomes in acute systemic inflammation. Sci Rep 4.  https://doi.org/10.1038/srep04347
  80. O’Flaherty R, Trbojević-Akmačić I, Greville G et al (2018) The sweet spot for biologics: recent advances in characterization of biotherapeutic glycoproteins. Expert Rev Proteomics 15:13–29.  https://doi.org/10.1080/14789450.2018.1404907CrossRefPubMedGoogle Scholar
  81. Olivieri F, Rippo MR, Monsurrò V et al (2013) MicroRNAs linking inflamm-aging, cellular senescence and cancer. Ageing Res. Rev. 12:1056–1068CrossRefGoogle Scholar
  82. Parekh RB, Dwek RA, Sutton BJ et al (1985) Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG. Nature 316:452–457.  https://doi.org/10.1038/316452a0CrossRefPubMedPubMedCentralGoogle Scholar
  83. Parekh R, Roitt I, Isenberg D et al (1988) Age-related galactosylation of the N-linked oligosaccharides of human serum IgG. J Exp Med 167:1731–1736.  https://doi.org/10.1084/jem.20142182CrossRefPubMedGoogle Scholar
  84. Pasek M, Duk M, Podbielska M et al (2006) Galactosylation of IgG from rheumatoid arthritis (RA) patients—changes during therapy. Glycoconj J 23:463–471.  https://doi.org/10.1007/s10719-006-5409-0CrossRefPubMedGoogle Scholar
  85. Pekelharing JM, Hepp E, Kamerling JP et al (1988) Alterations in carbohydrate composition of serum IgG from patients with rheumatoid arthritis and from pregnant women. Ann Rheum Dis 47:91–95.  https://doi.org/10.1136/ard.47.2.91CrossRefPubMedPubMedCentralGoogle Scholar
  86. Pezer M, Stambuk J, Perica M, et al (2016) Effects of allergic diseases and age on the composition of serum IgG glycome in children. Sci Rep 6.  https://doi.org/10.1038/srep33198
  87. PH S (1988) IgG subclasses. A historical perspective. Monogr Allergy 1–11Google Scholar
  88. Pincetic A, Bournazos S, DiLillo DJ et al (2014) Type I and type II Fc receptors regulate innate and adaptive immunity. Nat Immunol 15:707–716.  https://doi.org/10.1038/ni.2939CrossRefPubMedPubMedCentralGoogle Scholar
  89. Plomp R, Dekkers G, Rombouts Y et al (2015) Hinge-region O-glycosylation of human immunoglobulin G3 (IgG3). Mol Cell Proteomics 14:1373–1384.  https://doi.org/10.1074/mcp.m114.047381CrossRefPubMedPubMedCentralGoogle Scholar
  90. Plomp R, Ruhaak LR, Uh HW, et al (2017) Subclass-specific IgG glycosylation is associated with markers of inflammation and metabolic health. Sci Rep 7.  https://doi.org/10.1038/s41598-017-12495-0
  91. Pricer WE, Hudgin RL, Ashwell G et al (1974) [87] A membrane receptor protein for asialoglycoproteins. Methods Enzymol 34:688–691.  https://doi.org/10.1016/S0076-6879(74)34090-6CrossRefPubMedGoogle Scholar
  92. Pučić M, Knežević A, Vidič J et al (2011) High throughput isolation and glycosylation analysis of IgG—variability and heritability of the IgG Glycome in three isolated human populations. Mol Cell Proteomics 10(M111):010090.  https://doi.org/10.1074/mcp.M111.010090CrossRefPubMedGoogle Scholar
  93. Pučić M, Mužinić A, Novokmet M et al (2012) Changes in plasma and IgG N-glycome during childhood and adolescence. Glycobiology 22:975–982.  https://doi.org/10.1093/glycob/cws062CrossRefPubMedGoogle Scholar
  94. Raju TS (2008) Terminal sugars of Fc glycans influence antibody effector functions of IgGs. Curr Opin Immunol 20:471–478CrossRefGoogle Scholar
  95. Raju TS, Scallon BJ (2006) Glycosylation in the Fc domain of IgG increases resistance to proteolytic cleavage by papain. Biochem Biophys Res Commun 341:797–803.  https://doi.org/10.1016/j.bbrc.2006.01.030CrossRefPubMedGoogle Scholar
  96. Reusch D, Tejada ML (2015) Fc glycans of therapeutic antibodies as critical quality attributes. Glycobiology 25:1325–1334.  https://doi.org/10.1093/glycob/cwv065CrossRefPubMedPubMedCentralGoogle Scholar
  97. Rombouts Y, Willemze A, Van Beers JJBC et al (2016) Extensive glycosylation of ACPA-IgG variable domains modulates binding to citrullinated antigens in rheumatoid arthritis. Ann Rheum Dis 75:578–585.  https://doi.org/10.1136/annrheumdis-2014-206598CrossRefPubMedGoogle Scholar
  98. Rook GAW, Steele J, Brealey R et al (1991) Changes in IgG glycoform levels are associated with remission of arthritis during pregnancy. J Autoimmun 4:779–794.  https://doi.org/10.1016/0896-8411(91)90173-ACrossRefPubMedGoogle Scholar
  99. Ruhaak LR, Uh HW, Beekman M et al (2010) Decreased levels of bisecting GLcNAc glycoforms of IgG are associated with human longevity. PLoS ONE 5:1–8.  https://doi.org/10.1371/journal.pone.0012566CrossRefGoogle Scholar
  100. Ruhaak LR, Uh HW, Beekman M et al (2011) Plasma protein N-glycan profiles are associated with calendar age, familial longevity and health. J Proteome Res 10:1667–1674.  https://doi.org/10.1021/pr1009959CrossRefPubMedGoogle Scholar
  101. Russell D, Oldham NJ, Davis BG (2009) Site-selective chemical protein glycosylation protects from autolysis and proteolytic degradation. Carbohydr Res 344:1508–1514.  https://doi.org/10.1016/j.carres.2009.06.033CrossRefPubMedGoogle Scholar
  102. Sansoni P, Vescovini R, Fagnoni FF et al (2014) New advances in CMV and immunosenescence. Exp Gerontol 55:54–62.  https://doi.org/10.1016/j.exger.2014.03.020CrossRefPubMedGoogle Scholar
  103. Schwab I, Nimmerjahn F (2013) Intravenous immunoglobulin therapy: how does IgG modulate the immune system? Nat Rev Immunol 13:176–189CrossRefGoogle Scholar
  104. Seeling M, Bruckner C, Nimmerjahn F (2017) Differential antibody glycosylation in autoimmunity: sweet biomarker or modulator of disease activity? Nat Rev Rheumatol 13:621–630.  https://doi.org/10.1038/nrrheum.2017.146CrossRefPubMedGoogle Scholar
  105. Shields RL, Lai J, Keck R et al (2002) Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human FcγRIII and antibody-dependent cellular toxicity. J Biol Chem 277:26733–26740.  https://doi.org/10.1074/jbc.M202069200CrossRefPubMedGoogle Scholar
  106. Shikata K, Yasuda T, Takeuchi F et al (1998) Structural changes in the oligosaccharide moiety of human IgG with aging. Glycoconj J 15:683–689.  https://doi.org/10.1023/A:1006936431276CrossRefPubMedGoogle Scholar
  107. Shubhakar A, Reiding KR, Gardner RA et al (2014) High-throughput analysis and automation for glycomics studies. Chromatographia 78:321–333CrossRefGoogle Scholar
  108. Šimurina M, de Haan N, Vučković F et al (2018) Glycosylation of immunoglobulin G associates with clinical features of inflammatory bowel diseases. Gastroenterology 154:1320–1333.e10.  https://doi.org/10.1053/j.gastro.2018.01.002CrossRefPubMedPubMedCentralGoogle Scholar
  109. Spiegelberg HL, Fishkin BG (1972) The catabolism of human G immunoglobulins of different heavy chain subclasses. 3. The catabolism of heavy chain disease proteins and of Fc fragments of myeloma proteins. Clin Exp Immunol 10:599–607PubMedPubMedCentralGoogle Scholar
  110. Spiegelberg HL, Fishkin BG, Grey HM (1968) Catabolism of human gammaG-immunoglobulins of different heavy chain subclasses. I. Catabolism of gammaG-myeloma proteins in man. J Clin Invest 47:2323–2330.  https://doi.org/10.1172/JCI105917CrossRefPubMedPubMedCentralGoogle Scholar
  111. Stadlmann J, Pabst M, Altmann F (2010) Analytical and functional aspects of antibody sialylation. J. Clin. Immunol. 30Google Scholar
  112. Subedi GP, Barb AW (2015) The structural role of antibody N-glycosylation in receptor interactions. Structure 23:1573–1583.  https://doi.org/10.1016/j.str.2015.06.015CrossRefPubMedPubMedCentralGoogle Scholar
  113. Tei K, Kawakami-Kimura N, Taguchi O et al (2002) Roles of cell adhesion molecules in tumor angiogenesis induced by cotransplantation of cancer and endothelial cells to nude rats. Cancer Res 62:6289–6296.  https://doi.org/10.1158/0008-5472.can-03-3614CrossRefPubMedGoogle Scholar
  114. Theodoratou E, Thaci K, Agakov F et al (2016) Glycosylation of plasma IgG in colorectal cancer prognosis. Sci Rep 6:28098.  https://doi.org/10.1038/srep28098CrossRefPubMedPubMedCentralGoogle Scholar
  115. Trbojevic-Akmacic I, Vilaj M, Lauc G (2016) High-throughput analysis of immunoglobulin G glycosylation. Expert Rev Proteomics 13:523–534.  https://doi.org/10.1080/14789450.2016.1174584CrossRefPubMedGoogle Scholar
  116. Tsuchiya N, Endo T, Kochibe N et al (1998) Use of lectin for detection of agalactosyl IgG. Methods Mol Med 9:195–205.  https://doi.org/10.1385/0-89603-396-1:195CrossRefPubMedGoogle Scholar
  117. Van Beneden K, Coppieters K, Laroy W et al (2009) Reversible changes in serum immunoglobulin galactosylation during the immune response and treatment of inflammatory autoimmune arthritis. Ann Rheum Dis 68:1360–1365.  https://doi.org/10.1136/ard.2008.089292CrossRefPubMedGoogle Scholar
  118. van de Bovenkamp FS, Hafkenscheid L, Rispens T, Rombouts Y (2016) The emerging importance of IgG Fab glycosylation in immunity. J Immunol 196:1435–1441.  https://doi.org/10.4049/jimmunol.1502136CrossRefPubMedGoogle Scholar
  119. van de Bovenkamp FS, Derksen NIL, Ooijevaar-de Heer P et al (2018) Adaptive antibody diversification through N -linked glycosylation of the immunoglobulin variable region. Proc Natl Acad Sci 115:1901–1906.  https://doi.org/10.1073/pnas.1711720115CrossRefPubMedGoogle Scholar
  120. van de Geijn FE, Hazes JM, Geleijns K et al (2008) Mannose-binding lectin polymorphisms are not associated with rheumatoid arthritis—confirmation in two large cohorts. Rheumatol 47:1168–1171.  https://doi.org/10.1093/rheumatology/ken226CrossRefGoogle Scholar
  121. Van de Geijn FE, Wuhrer M, Selman MHJ, et al (2009) Immunoglobulin G galactosylation and sialylation are associated with pregnancy-induced improvement of rheumatoid arthritis and the postpartum flare: results from a large prospective cohort study. Arthritis Res Ther 11.  https://doi.org/10.1186/ar2892CrossRefGoogle Scholar
  122. van de Geijn FE, de Man YA, Wuhrer M et al (2011) Mannose-binding lectin does not explain the course and outcome of pregnancy in rheumatoid arthritis. Arthritis Res Ther 13:R10.  https://doi.org/10.1186/ar3231CrossRefPubMedPubMedCentralGoogle Scholar
  123. Vanhooren V, Desmyter L, Liu X-E et al (2007) N-glycomic changes in serum proteins during human aging. Rejuvenation Res 10:521–531a.  https://doi.org/10.1089/rej.2007.0556CrossRefPubMedGoogle Scholar
  124. Varki A (1993) Biological roles of oligosaccharides: all of the theories are correct. Glycobiology 3:97–130.  https://doi.org/10.1093/glycob/3.2.97CrossRefPubMedGoogle Scholar
  125. Varki A (2017) Biological roles of glycans. Glycobiology 27:3–49.  https://doi.org/10.1093/glycob/cww086CrossRefPubMedGoogle Scholar
  126. Varki A, Cummings RD, Esko JD et al (2015) Essentials of glycobiology. Cold Spring Harbor Laboratory Press, New YorkGoogle Scholar
  127. Vidarsson G, Dekkers G, Rispens T (2014) IgG subclasses and allotypes: from structure to effector functions. Front Immunol 5:520.  https://doi.org/10.3389/fimmu.2014.00520CrossRefPubMedPubMedCentralGoogle Scholar
  128. Wahl A, van den Akker E, Klaric L et al (2018) Genome-wide association study on immunoglobulin G glycosylation patterns. Front Immunol 9:277.  https://doi.org/10.3389/fimmu.2018.00277CrossRefPubMedPubMedCentralGoogle Scholar
  129. Wright A, Tao MH, Kabat EA, Morrison SL (1991) Antibody variable region glycosylation: position effects on antigen binding and carbohydrate structure. EMBO J 10:2717–23. doi: papers3://publication/uuid/E9934085-0F18-4037-81B4-AE2E0A42B40FGoogle Scholar
  130. Wuhrer M, Porcelijn L, Kapur R et al (2009) Regulated glycosylation patterns of IgG during alloimmune responses against human platelet antigens. J Proteome Res 8:450–456.  https://doi.org/10.1021/pr800651jCrossRefPubMedGoogle Scholar
  131. Yabe R, Tateno H, Hirabayashi J (2010) Frontal affinity chromatography analysis of constructs of DC-SIGN, DC-SIGNR and LSECtin extend evidence for affinity to agalactosylated N-glycans. FEBS J 277:4010–4026.  https://doi.org/10.1111/j.1742-4658.2010.07792.xCrossRefPubMedGoogle Scholar
  132. Yamada E, Tsukamoto Y, Sasaki R et al (1997) Structural changes of immunoglobulin G oligosaccharides with age in healthy human serum. Glycoconj J 14:401–405.  https://doi.org/10.1023/A:1018582930906CrossRefPubMedGoogle Scholar
  133. Yu X, Wang Y, Kristic J, et al (2016) Profiling IgG N-glycans as potential biomarker of chronological and biological ages: a community-based study in a Han Chinese population. Med (United States) 95.  https://doi.org/10.1097/md.0000000000004112CrossRefGoogle Scholar
  134. Zauner G, Selman MHJ, Bondt A et al (2013) Glycoproteomic analysis of antibodies. Mol Cell Proteomics 12:856–865.  https://doi.org/10.1074/mcp.r112.026005CrossRefPubMedPubMedCentralGoogle Scholar
  135. Zhang J, Lindsay LAL, Hedrick JL, Lebrilla CB (2004) Strategy for profiling and structure elucidation of mucin-type oligosaccharides by mass spectrometry. Anal Chem 76:5990–6001.  https://doi.org/10.1021/ac049666sCrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • M. Vilaj
    • 1
  • I. Gudelj
    • 1
  • I. Trbojević-Akmačić
    • 1
  • G. Lauc
    • 1
    • 2
  • M. Pezer
    • 1
    Email author
  1. 1.Genos Glycoscience Research LaboratoryZagrebCroatia
  2. 2.Faculty of Pharmacy and BiochemistryUniversity of ZagrebZagrebCroatia

Personalised recommendations