Regulation of antibody effector functions through IgG Fc N-glycosylation

Cellular and Molecular Life Sciences

Volumn 74, Issue 5, 2017, Pages 837-847

  Quast, Isaak ^a   Peschke, Benjamin ^a   Lünemann, Jan D ^a  

^a UNIVERSITY OF ZURICH   (Switzerland)

Author keywords

Antibody; Glycan; Glycobiology; Immunoglobulin; Immunology; Immunotherapy

Indexed keywords

CD16 ANTIGEN; CD64 ANTIGEN; FC RECEPTOR; FC RECEPTOR IIA; FC RECEPTOR IIB; FUCOSE; GALACTOSE; IMMUNOGLOBULIN G; IMMUNOGLOBULIN G ANTIBODY; SIALIC ACID; COMPLEMENT; IMMUNOGLOBULIN FC FRAGMENT; POLYSACCHARIDE;

ANTIBODY EFFECTOR FUNCTION; COMPLEMENT ACTIVATION; CONFORMATIONAL TRANSITION; CRYSTALLIZABLE FRAGMENT; HUMAN; NONHUMAN; PHAGOCYTOSIS; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN GLYCOSYLATION; PROTEIN STRUCTURE; RECEPTOR BINDING; REVIEW; ANIMAL; CHEMISTRY; GLYCOSYLATION; METABOLISM;

ANIMALS; COMPLEMENT SYSTEM PROTEINS; GLYCOSYLATION; HUMANS; IMMUNOGLOBULIN FC FRAGMENTS; IMMUNOGLOBULIN G; POLYSACCHARIDES;

EID: 84988433855     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-016-2366-z     Document Type: Review

References (99)

1. Woof JM, Russell MW (2011) Structure and function relationships in IgA. Mucosal Immunol 4(6):590–597
2. Vidarsson G, Dekkers G, Rispens T (2014) IgG subclasses and allotypes: from structure to effector functions. Front Immunol 5:520. doi:10.3389/fimmu.2014.00520
3. Anderson NL, Anderson NG (2002) The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteom 1(11):845–867
4. Pone EJ, Zhang J, Mai T, White CA, Li G, Sakakura JK, Patel PJ, Al-Qahtani A, Zan H, Xu Z, Casali P (2012) BCR-signalling synergizes with TLR-signalling for induction of AID and immunoglobulin class-switching through the non-canonical NF-kappaB pathway. Nat Commun 3:767. doi:10.1038/ncomms1769
5. Arnold JN, Wormald MR, Sim RB, Rudd PM, Dwek RA (2007) The impact of glycosylation on the biological function and structure of human immunoglobulins. Annu Rev Immunol 25:21–50. doi:10.1146/annurev.immunol.25.022106.141702
6. Quast I, Lunemann JD (2014) Fc glycan-modulated immunoglobulin G effector functions. J Clin Immunol 34(Suppl 1):S51–S55. doi:10.1007/s10875-014-0018-3
7. Chaudhury C, Mehnaz S, Robinson JM, Hayton WL, Pearl DK, Roopenian DC, Anderson CL (2003) The major histocompatibility complex-related Fc receptor for IgG (FcRn) binds albumin and prolongs its lifespan. J Exp Med 197(3):315–322
8. Ober RJ, Martinez C, Vaccaro C, Zhou J, Ward ES (2004) Visualizing the site and dynamics of IgG salvage by the MHC class I-related receptor. FcRn. J Immunol 172(4):2021–2029
9. Dickinson BL, Badizadegan K, Wu Z, Ahouse JC, Zhu X, Simister NE, Blumberg RS, Lencer WI (1999) Bidirectional FcRn-dependent IgG transport in a polarized human intestinal epithelial cell line. J Clin Invest 104(7):903–911. doi:10.1172/JCI6968
10. Roux KH, Strelets L, Michaelsen TE (1997) Flexibility of human IgG subclasses. J Immunol 159(7):3372–3382
11. Lefranc MP, Lefranc G (2012) Human Gm, Km, and Am allotypes and their molecular characterization: a remarkable demonstration of polymorphism. Methods Mol Biol 882:635–680. doi:10.1007/978-1-61779-842-9_34
12. Ernst LK, Metes D, Herberman RB, Morel PA (2002) Allelic polymorphisms in the FcgammaRIIC gene can influence its function on normal human natural killer cells. J Mol Med (Berl) 80(4):248–257. doi:10.1007/s00109-001-0294-2
13. Duncan AR, Woof JM, Partridge LJ, Burton DR, Winter G (1988) Localization of the binding site for the human high-affinity Fc receptor on IgG. Nature 332(6164):563–564. doi:10.1038/332563a0
14. Chappel MS, Isenman DE, Everett M, Xu YY, Dorrington KJ, Klein MH (1991) Identification of the Fc gamma receptor class I binding site in human IgG through the use of recombinant IgG1/IgG2 hybrid and point-mutated antibodies. Proc Natl Acad Sci USA 88(20):9036–9040
15. Sondermann P, Huber R, Oosthuizen V, Jacob U (2000) The 3.2-A crystal structure of the human IgG1 Fc fragment-Fc gammaRIII complex. Nature 406(6793):267–273. doi:10.1038/35018508
16. Ierino FL, Hulett MD, McKenzie IF, Hogarth PM (1993) Mapping epitopes of human Fc gamma RII (CDw32) with monoclonal antibodies and recombinant receptors. J Immunol 150(5):1794–1803
17. Canfield SM, Morrison SL (1991) The binding affinity of human IgG for its high affinity Fc receptor is determined by multiple amino acids in the CH2 domain and is modulated by the hinge region. J Exp Med 173(6):1483–1491
18. Kaneko Y, Nimmerjahn F, Ravetch JV (2006) Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation. Science 313(5787):670–673. doi:10.1126/science.1129594
19. Shields RL, Lai J, Keck R, O’Connell LY, Hong K, Meng YG, Weikert SH, Presta LG (2002) Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human Fcgamma RIII and antibody-dependent cellular toxicity. J Biol Chem 277(30):26733–26740. doi:10.1074/jbc.M202069200
20. Bruhns P, Iannascoli B, England P, Mancardi DA, Fernandez N, Jorieux S, Daeron M (2009) Specificity and affinity of human Fcgamma receptors and their polymorphic variants for human IgG subclasses. Blood 113(16):3716–3725. doi:10.1182/blood-2008-09-179754
21. van der Poel CE, Spaapen RM, van de Winkel JG, Leusen JH (2011) Functional characteristics of the high affinity IgG receptor, FcgammaRI. J Immunol 186(5):2699–2704. doi:10.4049/jimmunol.1003526
22. Miller KL, Duchemin AM, Anderson CL (1996) A novel role for the Fc receptor gamma subunit: enhancement of Fc gamma R ligand affinity. J Exp Med 183(5):2227–2233
23. Sondermann P, Jacob U, Kutscher C, Frey J (1999) Characterization and crystallization of soluble human Fc gamma receptor II (CD32) isoforms produced in insect cells. Biochemistry 38(26):8469–8477. doi:10.1021/bi982889q
24. Vance BA, Huizinga TW, Wardwell K, Guyre PM (1993) Binding of monomeric human IgG defines an expression polymorphism of Fc gamma RIII on large granular lymphocyte/natural killer cells. J Immunol 151(11):6429–6439
25. Li P, Jiang N, Nagarajan S, Wohlhueter R, Selvaraj P, Zhu C (2007) Affinity and kinetic analysis of Fcgamma receptor IIIa (CD16a) binding to IgG ligands. J Biol Chem 282(9):6210–6221. doi:10.1074/jbc.M609064200
26. Tanaka M, Krutzik SR, Sieling PA, Lee DJ, Rea TH, Modlin RL (2009) Activation of Fc gamma RI on monocytes triggers differentiation into immature dendritic cells that induce autoreactive T cell responses. J Immunol 183(4):2349–2355. doi:10.4049/jimmunol.0801683
27. Quast I, Cueni F, Nimmerjahn F, Tackenberg B, Lunemann JD (2015) Deregulated Fcgamma receptor expression in patients with CIDP. Neurol Neuroimmunol Neuroinflamm 2(5):e148. doi:10.1212/NXI.0000000000000148
28. Kikuchi-Taura A, Yura A, Tsuji S, Ohshima S, Kitatoube A, Shimizu T, Nii T, Katayama M, Teshigawara S, Yoshimura M, Kudo-Tanaka E, Harada Y, Matsushita M, Hashimoto J, Saeki Y (2015) Monocyte CD64 expression as a novel biomarker for the disease activity of systemic lupus erythematosus. Lupus. doi:10.1177/0961203315579093
29. Harrison PT, Davis W, Norman JC, Hockaday AR, Allen JM (1994) Binding of monomeric immunoglobulin G triggers Fc gamma RI-mediated endocytosis. J Biol Chem 269(39):24396–24402
30. Mancardi DA, Albanesi M, Jonsson F, Iannascoli B, Van Rooijen N, Kang X, England P, Daeron M, Bruhns P (2013) The high-affinity human IgG receptor FcgammaRI (CD64) promotes IgG-mediated inflammation, anaphylaxis, and antitumor immunotherapy. Blood 121(9):1563–1573. doi:10.1182/blood-2012-07-442541
31. King M, McDermott P, Schreiber AD (1990) Characterization of the Fc gamma receptor on human platelets. Cell Immunol 128(2):462–479
32. Veri MC, Gorlatov S, Li H, Burke S, Johnson S, Stavenhagen J, Stein KE, Bonvini E, Koenig S (2007) Monoclonal antibodies capable of discriminating the human inhibitory Fcgamma-receptor IIB (CD32B) from the activating Fcgamma-receptor IIA (CD32A): biochemical, biological and functional characterization. Immunology 121(3):392–404. doi:10.1111/j.1365-2567.2007.02588.x
33. Metes D, Ernst LK, Chambers WH, Sulica A, Herberman RB, Morel PA (1998) Expression of functional CD32 molecules on human NK cells is determined by an allelic polymorphism of the FcgammaRIIC gene. Blood 91(7):2369–2380
34. Ravetch JV, Perussia B (1989) Alternative membrane forms of Fc gamma RIII(CD16) on human natural killer cells and neutrophils. Cell type-specific expression of two genes that differ in single nucleotide substitutions. J Exp Med 170(2):481–497
35. Edberg JC, Barinsky M, Redecha PB, Salmon JE, Kimberly RP (1990) Fc gamma RIII expressed on cultured monocytes is a N-glycosylated transmembrane protein distinct from Fc gamma RIII expressed on natural killer cells. J Immunol 144(12):4729–4734
36. Li F, Smith P, Ravetch JV (2014) Inhibitory Fcgamma receptor is required for the maintenance of tolerance through distinct mechanisms. J Immunol 192(7):3021–3028. doi:10.4049/jimmunol.1302934
37. Bolland S, Ravetch JV (2000) Spontaneous autoimmune disease in Fc(gamma)RIIB-deficient mice results from strain-specific epistasis. Immunity 13(2):277–285
38. Tackenberg B, Jelcic I, Baerenwaldt A, Oertel WH, Sommer N, Nimmerjahn F, Lunemann JD (2009) Impaired inhibitory Fcgamma receptor IIB expression on B cells in chronic inflammatory demyelinating polyneuropathy. Proc Natl Acad Sci USA 106(12):4788–4792. doi:10.1073/pnas.0807319106
39. Mackay M, Stanevsky A, Wang T, Aranow C, Li M, Koenig S, Ravetch JV, Diamond B (2006) Selective dysregulation of the FcgammaIIB receptor on memory B cells in SLE. J Exp Med 203(9):2157–2164. doi:10.1084/jem.20051503
40. Xiang Z, Cutler AJ, Brownlie RJ, Fairfax K, Lawlor KE, Severinson E, Walker EU, Manz RA, Tarlinton DM, Smith KG (2007) FcgammaRIIb controls bone marrow plasma cell persistence and apoptosis. Nat Immunol 8(4):419–429. doi:10.1038/ni1440
41. Fukuyama H, Nimmerjahn F, Ravetch JV (2005) The inhibitory Fcgamma receptor modulates autoimmunity by limiting the accumulation of immunoglobulin G+ anti-DNA plasma cells. Nat Immunol 6(1):99–106. doi:10.1038/ni1151
42. Boruchov AM, Heller G, Veri MC, Bonvini E, Ravetch JV, Young JW (2005) Activating and inhibitory IgG Fc receptors on human DCs mediate opposing functions. J Clin Invest 115(10):2914–2923. doi:10.1172/jci24772
43. Clynes R, Maizes JS, Guinamard R, Ono M, Takai T, Ravetch JV (1999) Modulation of immune complex-induced inflammation in vivo by the coordinate expression of activation and inhibitory Fc receptors. J Exp Med 189(1):179–185
44. Gaboriaud C, Juanhuix J, Gruez A, Lacroix M, Darnault C, Pignol D, Verger D, Fontecilla-Camps JC, Arlaud GJ (2003) The crystal structure of the globular head of complement protein C1q provides a basis for its versatile recognition properties. J Biol Chem 278(47):46974–46982. doi:10.1074/jbc.M307764200
45. Duncan AR, Winter G (1988) The binding site for C1q on IgG. Nature 332(6166):738–740. doi:10.1038/332738a0
46. Malhotra R, Wormald MR, Rudd PM, Fischer PB, Dwek RA, Sim RB (1995) Glycosylation changes of IgG associated with rheumatoid arthritis can activate complement via the mannose-binding protein. Nat Med 1(3):237–243
47. Nimmerjahn F, Anthony RM, Ravetch JV (2007) Agalactosylated IgG antibodies depend on cellular Fc receptors for in vivo activity. Proc Natl Acad Sci USA 104(20):8433–8437. doi:10.1073/pnas.0702936104
48. Shohet JM, Pemberton P, Carroll MC (1993) Identification of a major binding site for complement C3 on the IgG1 heavy chain. J Biol Chem 268(8):5866–5871
49. Tao MH, Smith RI, Morrison SL (1993) Structural features of human immunoglobulin G that determine isotype-specific differences in complement activation. J Exp Med 178(2):661–667
50. Idusogie EE, Presta LG, Gazzano-Santoro H, Totpal K, Wong PY, Ultsch M, Meng YG, Mulkerrin MG (2000) Mapping of the C1q binding site on rituxan, a chimeric antibody with a human IgG1 Fc. J Immunol 164(8):4178–4184
51. Brekke OH, Michaelsen TE, Aase A, Sandin RH, Sandlie I (1994) Human IgG isotype-specific amino acid residues affecting complement-mediated cell lysis and phagocytosis. Eur J Immunol 24(10):2542–2547. doi:10.1002/eji.1830241042
52. Schwarz F, Aebi M (2011) Mechanisms and principles of N-linked protein glycosylation. Curr Opin Struct Biol 21(5):576–582. doi:10.1016/j.sbi.2011.08.005
53. Moremen KW, Tiemeyer M, Nairn AV (2012) Vertebrate protein glycosylation: diversity, synthesis and function. Nat Rev Mol Cell Biol 13(7):448–462. doi:10.1038/nrm3383
54. Parekh R, Roitt I, Isenberg D, Dwek R, Rademacher T (1988) Age-related galactosylation of the N-linked oligosaccharides of human serum IgG. J Exp Med 167(5):1731–1736
55. Parekh RB, Dwek RA, Sutton BJ, Fernandes DL, Leung A, Stanworth D, Rademacher TW, Mizuochi T, Taniguchi T, Matsuta K et al (1985) Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG. Nature 316(6027):452–457
56. Mizuochi T, Taniguchi T, Shimizu A, Kobata A (1982) Structural and numerical variations of the carbohydrate moiety of immunoglobulin G. J Immunol 129(5):2016–2020
57. Shikata K, Yasuda T, Takeuchi F, Konishi T, Nakata M, Mizuochi T (1998) Structural changes in the oligosaccharide moiety of human IgG with aging. Glycoconj J 15(7):683–689
58. Zauner G, Selman MH, Bondt A, Rombouts Y, Blank D, Deelder AM, Wuhrer M (2013) Glycoproteomic analysis of antibodies. Mol Cell Proteom 12(4):856–865. doi:10.1074/mcp.R112.026005
59. Wuhrer M, Stam JC, van de Geijn FE, Koeleman CA, Verrips CT, Dolhain RJ, Hokke CH, Deelder AM (2007) Glycosylation profiling of immunoglobulin G (IgG) subclasses from human serum. Proteomics 7(22):4070–4081. doi:10.1002/pmic.200700289
60. Wormald MR, Rudd PM, Harvey DJ, Chang SC, Scragg IG, Dwek RA (1997) Variations in oligosaccharide-protein interactions in immunoglobulin G determine the site-specific glycosylation profiles and modulate the dynamic motion of the Fc oligosaccharides. Biochemistry 36(6):1370–1380. doi:10.1021/bi9621472
61. Holland M, Yagi H, Takahashi N, Kato K, Savage CO, Goodall DM, Jefferis R (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 1760(4):669–677. doi:10.1016/j.bbagen.2005.11.021
62. Jefferis R (2005) Glycosylation of recombinant antibody therapeutics. Biotechnol Prog 21(1):11–16. doi:10.1021/bp040016j
63. van de Bovenkamp FS, Hafkenscheid L, Rispens T, Rombouts Y (2016) The emerging importance of IgG Fab glycosylation in immunity. J Immunol 196(4):1435–1441. doi:10.4049/jimmunol.1502136
64. Nose M, Wigzell H (1983) Biological significance of carbohydrate chains on monoclonal antibodies. Proc Natl Acad Sci USA 80(21):6632–6636
65. Herter S, Birk MC, Klein C, Gerdes C, Umana P, Bacac M (2014) Glycoengineering of therapeutic antibodies enhances monocyte/macrophage-mediated phagocytosis and cytotoxicity. J Immunol 192(5):2252–2260. doi:10.4049/jimmunol.1301249
66. Golay J, Da Roit F, Bologna L, Ferrara C, Leusen JH, Rambaldi A, Klein C, Introna M (2013) Glycoengineered CD20 antibody obinutuzumab activates neutrophils and mediates phagocytosis through CD16B more efficiently than rituximab. Blood 122(20):3482–3491. doi:10.1182/blood-2013-05-504043
67. Niwa R, Hatanaka S, Shoji-Hosaka E, Sakurada M, Kobayashi Y, Uehara A, Yokoi H, Nakamura K, Shitara K (2004) Enhancement of the antibody-dependent cellular cytotoxicity of low-fucose IgG1 Is independent of FcgammaRIIIa functional polymorphism. Clin Cancer Res 10(18 Pt 1):6248–6255. doi:10.1158/1078-0432.ccr-04-0850
68. Mori K, Iida S, Yamane-Ohnuki N, Kanda Y, Kuni-Kamochi R, Nakano R, Imai-Nishiya H, Okazaki A, Shinkawa T, Natsume A, Niwa R, Shitara K, Satoh M (2007) Non-fucosylated therapeutic antibodies: the next generation of therapeutic antibodies. Cytotechnology 55(2–3):109–114. doi:10.1007/s10616-007-9103-2
69. Gasdaska JR, Sherwood S, Regan JT, Dickey LF (2012) An afucosylated anti-CD20 monoclonal antibody with greater antibody-dependent cellular cytotoxicity and B-cell depletion and lower complement-dependent cytotoxicity than rituximab. Mol Immunol 50(3):134–141. doi:10.1016/j.molimm.2012.01.001
70. Anthony RM, Nimmerjahn F, Ashline DJ, Reinhold VN, Paulson JC, Ravetch JV (2008) Recapitulation of IVIG anti-inflammatory activity with a recombinant IgG Fc. Science 320(5874):373–376. doi:10.1126/science.1154315
71. Rademacher TW, Williams P, Dwek RA (1994) Agalactosyl glycoforms of IgG autoantibodies are pathogenic. Proc Natl Acad Sci USA 91(13):6123–6127
72. Bond A, Alavi A, Axford JS, Bourke BE, Bruckner FE, Kerr MA, Maxwell JD, Tweed KJ, Weldon MJ, Youinou P, Hay FC (1997) A detailed lectin analysis of IgG glycosylation, demonstrating disease specific changes in terminal galactose and N-acetylglucosamine. J Autoimmun 10(1):77–85. doi:10.1006/jaut.1996.0104
73. Vuckovic F, Kristic J, Gudelj I, Teruel M, Keser T, Pezer M, Pucic-Bakovic M, Stambuk J, Trbojevic-Akmacic I, Barrios C, Pavic T, Menni C, Wang Y, Zhou Y, Cui L, Song H, Zeng Q, Guo X, Pons-Estel BA, McKeigue P, Leslie Patrick A, Gornik O, Spector TD, Harjacek M, Alarcon-Riquelme M, Molokhia M, Wang W, Lauc G (2015) Association of systemic lupus erythematosus with decreased immunosuppressive potential of the IgG glycome. Arthritis Rheumatol (Hoboken, NJ) 67(11):2978–2989. doi:10.1002/art.39273
74. Wuhrer M, Selman MHJ, McDonnell LA, Kümpfel T, Derfuss T, Khademi M, Olsson T, Hohlfeld R, Meinl E, Krumbholz M (2015) Pro-inflammatory pattern of IgG1 Fc glycosylation in multiple sclerosis cerebrospinal fluid. J Neuroinflamm 12(1):1–14. doi:10.1186/s12974-015-0450-1
75. Rook GA, Steele J, Brealey R, Whyte A, Isenberg D, Sumar N, Nelson JL, Bodman KB, Young A, Roitt IM et al (1991) Changes in IgG glycoform levels are associated with remission of arthritis during pregnancy. J Autoimmun 4(5):779–794
76. Bondt A, Selman MH, Deelder AM, Hazes JM, Willemsen SP, Wuhrer M, Dolhain RJ (2013) Association between galactosylation of immunoglobulin G and improvement of rheumatoid arthritis during pregnancy is independent of sialylation. J Proteome Res 12(10):4522–4531. doi:10.1021/pr400589m
77. Karsten CM, Pandey MK, Figge J, Kilchenstein R, Taylor PR, Rosas M, McDonald JU, Orr SJ, Berger M, Petzold D, Blanchard V, Winkler A, Hess C, Reid DM, Majoul IV, Strait RT, Harris NL, Kohl G, Wex E, Ludwig R, Zillikens D, Nimmerjahn F, Finkelman FD, Brown GD, Ehlers M, Kohl J (2012) Anti-inflammatory activity of IgG1 mediated by Fc galactosylation and association of FcgammaRIIB and dectin-1. Nat Med 18(9):1401–1406. doi:10.1038/nm.2862
78. Ackerman ME, Crispin M, Yu X, Baruah K, Boesch AW, Harvey DJ, Dugast AS, Heizen EL, Ercan A, Choi I, Streeck H, Nigrovic PA, Bailey-Kellogg C, Scanlan C, Alter G (2013) Natural variation in Fc glycosylation of HIV-specific antibodies impacts antiviral activity. J Clin Invest 123(5):2183–2192. doi:10.1172/jci65708
79. Ho CH, Chien RN, Cheng PN, Liu JH, Liu CK, Su CS, Wu IC, Li IC, Tsai HW, Wu SL, Liu WC, Chen SH, Chang TT (2015) Aberrant serum immunoglobulin G glycosylation in chronic hepatitis B is associated with histological liver damage and reversible by antiviral therapy. J Infect Dis 211(1):115–124. doi:10.1093/infdis/jiu388
80. Parekh RB, Roitt IM, Isenberg DA, Dwek RA, Ansell BM, Rademacher TW (1988) Galactosylation of IgG associated oligosaccharides: reduction in patients with adult and juvenile onset rheumatoid arthritis and relation to disease activity. Lancet (London, England) 1 (8592):966–969
81. Scherer HU, van der Woude D, Ioan-Facsinay A, el Bannoudi H, Trouw LA, Wang J, Haupl T, Burmester GR, Deelder AM, Huizinga TW, Wuhrer M, Toes RE (2010) Glycan profiling of anti-citrullinated protein antibodies isolated from human serum and synovial fluid. Arthritis Rheum 62(6):1620–1629. doi:10.1002/art.27414
82. Espy C, Morelle W, Kavian N, Grange P, Goulvestre C, Viallon V, Chereau C, Pagnoux C, Michalski JC, Guillevin L, Weill B, Batteux F, Guilpain P (2011) Sialylation levels of anti-proteinase 3 antibodies are associated with the activity of granulomatosis with polyangiitis (Wegener’s). Arthritis Rheum 63(7):2105–2115. doi:10.1002/art.30362
83. van de Geijn FE, Wuhrer M, Selman MH, Willemsen SP, de Man YA, Deelder AM, Hazes JM, Dolhain RJ (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(6):R193. doi:10.1186/ar2892
84. Washburn N, Schwab I, Ortiz D, Bhatnagar N, Lansing JC, Medeiros A, Tyler S, Mekala D, Cochran E, Sarvaiya H, Garofalo K, Meccariello R, Meador JW 3rd, Rutitzky L, Schultes BC, Ling L, Avery W, Nimmerjahn F, Manning AM, Kaundinya GV, Bosques CJ (2015) Controlled tetra-Fc sialylation of IVIg results in a drug candidate with consistent enhanced anti-inflammatory activity. Proc Natl Acad Sci USA 112(11):E1297–E1306. doi:10.1073/pnas.1422481112
85. Anthony RM, Kobayashi T, Wermeling F, Ravetch JV (2011) Intravenous gammaglobulin suppresses inflammation through a novel T(H)2 pathway. Nature 475(7354):110–113. doi:10.1038/nature10134
86. Yu X, Vasiljevic S, Mitchell DA, Crispin M, Scanlan CN (2013) Dissecting the molecular mechanism of IVIg therapy: the interaction between serum IgG and DC-SIGN is independent of antibody glycoform or Fc domain. J Mol Biol 425(8):1253–1258. doi:10.1016/j.jmb.2013.02.006
87. Anthony RM, Wermeling F, Karlsson MC, Ravetch JV (2008) Identification of a receptor required for the anti-inflammatory activity of IVIG. Proc Natl Acad Sci USA 105(50):19571–19578. doi:10.1073/pnas.0810163105
88. Bayry J, Bansal K, Kazatchkine MD, Kaveri SV (2009) DC-SIGN and α2,6-sialylated IgG Fc interaction is dispensable for the anti-inflammatory activity of IVIg on human dendritic cells. Proc Natl Acad Sci 106(9):E24. doi:10.1073/pnas.0900016106
89. Quast I, Keller CW, Maurer MA, Giddens JP, Tackenberg B, Wang LX, Munz C, Nimmerjahn F, Dalakas MC, Lunemann JD (2015) Sialylation of IgG Fc domain impairs complement-dependent cytotoxicity. J Clin Invest 125(11):4160–4170. doi:10.1172/JCI82695
90. Sehn LH, Goy A, Offner FC, Martinelli G, Caballero MD, Gadeberg O, Baetz T, Zelenetz AD, Gaidano G, Fayad LE, Buckstein R, Friedberg JW, Crump M, Jaksic B, Zinzani PL, Padmanabhan Iyer S, Sahin D, Chai A, Fingerle-Rowson G, Press OW (2015) Randomized phase II trial comparing obinutuzumab (GA101) with rituximab in patients with relapsed CD20+ indolent B-cell non-Hodgkin lymphoma: final analysis of the GAUSS study. J Clin Oncol 33(30):3467–3474. doi:10.1200/jco.2014.59.2139
91. Albert H, Collin M, Dudziak D, Ravetch JV, Nimmerjahn F (2008) In vivo enzymatic modulation of IgG glycosylation inhibits autoimmune disease in an IgG subclass-dependent manner. Proc Natl Acad Sci USA 105(39):15005–15009. doi:10.1073/pnas.0808248105
92. Benkhoucha M, Molnarfi N, Santiago-Raber ML, Weber MS, Merkler D, Collin M, Lalive PH (2012) IgG glycan hydrolysis by EndoS inhibits experimental autoimmune encephalomyelitis. J Neuroinflamm 9:209. doi:10.1186/1742-2094-9-209
93. Hirose M, Vafia K, Kalies K, Groth S, Westermann J, Zillikens D, Ludwig RJ, Collin M, Schmidt E (2012) Enzymatic autoantibody glycan hydrolysis alleviates autoimmunity against type VII collagen. J Autoimmun 39(4):304–314. doi:10.1016/j.jaut.2012.04.002
94. Nandakumar KS, Collin M, Olsen A, Nimmerjahn F, Blom AM, Ravetch JV, Holmdahl R (2007) Endoglycosidase treatment abrogates IgG arthritogenicity: importance of IgG glycosylation in arthritis. Eur J Immunol 37(10):2973–2982. doi:10.1002/eji.200737581
95. Collin M, Shannon O, Bjorck L (2008) IgG glycan hydrolysis by a bacterial enzyme as a therapy against autoimmune conditions. Proc Natl Acad Sci USA 105(11):4265–4270. doi:10.1073/pnas.0711271105
96. Lood C, Allhorn M, Lood R, Gullstrand B, Olin AI, Ronnblom L, Truedsson L, Collin M, Bengtsson AA (2012) IgG glycan hydrolysis by endoglycosidase S diminishes the proinflammatory properties of immune complexes from patients with systemic lupus erythematosus: a possible new treatment? Arthritis Rheum 64(8):2698–2706. doi:10.1002/art.34454
97. Schwab I, Mihai S, Seeling M, Kasperkiewicz M, Ludwig RJ, Nimmerjahn F (2014) Broad requirement for terminal sialic acid residues and FcgammaRIIB for the preventive and therapeutic activity of intravenous immunoglobulins in vivo. Eur J Immunol 44(5):1444–1453. doi:10.1002/eji.201344230
98. Schwab I, Lux A, Nimmerjahn F (2015) Pathways responsible for human autoantibody and therapeutic intravenous IgG activity in humanized mice. Cell Rep 13(3):610–620. doi:10.1016/j.celrep.2015.09.013
99. Hess C, Winkler A, Lorenz AK, Holecska V, Blanchard V, Eiglmeier S, Schoen AL, Bitterling J, Stoehr AD, Petzold D, Schommartz T, Mertes MM, Schoen CT, Tiburzy B, Herrmann A, Kohl J, Manz RA, Madaio MP, Berger M, Wardemann H, Ehlers M (2013) T cell-independent B cell activation induces immunosuppressive sialylated IgG antibodies. J Clin Invest 123(9):3788–3796. doi:10.1172/jci65938