Estrogen-Driven Changes in Immunoglobulin G Fc Glycosylation

Overview

Journal Exp Suppl

Specialties General Medicine
Science

Date 2021 Oct 23

PMID 34687016

Citations 8

Authors

Kaitlyn A Lagattuta

Peter A Nigrovic

Affiliations

Soon will be listed here.

Abstract

Glycosylation within the immunoglobulin G (IgG) Fc region modulates its ability to engage complement and Fc receptors, affording the opportunity to fine-tune effector functions. Mechanisms regulating IgG Fc glycans remain poorly understood. Changes accompanying menarche, menopause, and pregnancy have long implicated hormonal factors. Intervention studies now confirm that estrogens enhance IgG Fc galactosylation, in females and also in males, defining the first pathway modulating Fc glycans and thereby a new link between sex and immunity. This mechanism may participate in fetal-maternal immunity, antibody-mediated inflammation, and other aspects of age- and sex-specific immune function. Here we review the changes affecting the IgG Fc glycome from childhood through old age, the evidence establishing a role for estrogens, and research directions to uncover associated mechanisms that may inform therapeutic intervention.

Citing Articles

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References

Abbassi-Ghanavati M, Greer L, Cunningham F . Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol. 2009; 114(6):1326-1331. DOI: 10.1097/AOG.0b013e3181c2bde8. View

Ackerman M, Crispin M, Yu X, Baruah K, Boesch A, Harvey D . Natural variation in Fc glycosylation of HIV-specific antibodies impacts antiviral activity. J Clin Invest. 2013; 123(5):2183-92. PMC: 3637034. DOI: 10.1172/JCI65708. View

Arnold J, Dwek R, Rudd P, Sim R . Mannan binding lectin and its interaction with immunoglobulins in health and in disease. Immunol Lett. 2006; 106(2):103-10. DOI: 10.1016/j.imlet.2006.05.007. View

Axford J, Mackenzie L, Lydyard P, Hay F, Isenberg D, Roitt I . Reduced B-cell galactosyltransferase activity in rheumatoid arthritis. Lancet. 1987; 2(8574):1486-8. DOI: 10.1016/s0140-6736(87)92621-3. View

Bae S, Choi J . Tumor suppressor activity of RUNX3. Oncogene. 2004; 23(24):4336-40. DOI: 10.1038/sj.onc.1207286. View

Bakovic M, Selman M, Hoffmann M, Rudan I, Campbell H, Deelder A . High-throughput IgG Fc N-glycosylation profiling by mass spectrometry of glycopeptides. J Proteome Res. 2013; 12(2):821-31. DOI: 10.1021/pr300887z. View

Banda N, Wood A, Takahashi K, Levitt B, Rudd P, Royle L . Initiation of the alternative pathway of murine complement by immune complexes is dependent on N-glycans in IgG antibodies. Arthritis Rheum. 2008; 58(10):3081-9. PMC: 2574875. DOI: 10.1002/art.23865. View

Barb A, Prestegard J . NMR analysis demonstrates immunoglobulin G N-glycans are accessible and dynamic. Nat Chem Biol. 2011; 7(3):147-53. PMC: 3074608. DOI: 10.1038/nchembio.511. View

Barreto-Andrade J, de Fatima L, Campello R, Guedes J, de Freitas H, Machado M . Estrogen Receptor 1 (ESR1) Enhances /GLUT4 Expression by a SP1 Cooperative Mechanism. Int J Med Sci. 2018; 15(12):1320-1328. PMC: 6158671. DOI: 10.7150/ijms.26774. View

10.

Bartella V, Rizza P, Barone I, Zito D, Giordano F, Giordano C . Estrogen receptor beta binds Sp1 and recruits a corepressor complex to the estrogen receptor alpha gene promoter. Breast Cancer Res Treat. 2012; 134(2):569-81. PMC: 4484599. DOI: 10.1007/s10549-012-2090-9. View

11.

Bidlingmaier F, Butenandt O, Knorr D . Plasma estrogens in childhood and puberty under physiologic and pathologic conditions. Pediatr Res. 1973; 7(11):901-7. DOI: 10.1203/00006450-197311000-00006. View

12.

Bondt A, Selman M, Deelder A, Hazes J, Willemsen S, Wuhrer M . Association between galactosylation of immunoglobulin G and improvement of rheumatoid arthritis during pregnancy is independent of sialylation. J Proteome Res. 2013; 12(10):4522-31. DOI: 10.1021/pr400589m. View

13.

Bondt A, Rombouts Y, Selman M, Hensbergen P, Reiding K, Hazes J . Immunoglobulin G (IgG) Fab glycosylation analysis using a new mass spectrometric high-throughput profiling method reveals pregnancy-associated changes. Mol Cell Proteomics. 2014; 13(11):3029-39. PMC: 4223489. DOI: 10.1074/mcp.M114.039537. View

14.

Borghi S, Bournazos S, Thulin N, Li C, Gajewski A, Sherwood R . FcRn, but not FcγRs, drives maternal-fetal transplacental transport of human IgG antibodies. Proc Natl Acad Sci U S A. 2020; 117(23):12943-12951. PMC: 7293622. DOI: 10.1073/pnas.2004325117. View

15.

Bourdeau V, Deschenes J, Metivier R, Nagai Y, Nguyen D, Bretschneider N . Genome-wide identification of high-affinity estrogen response elements in human and mouse. Mol Endocrinol. 2004; 18(6):1411-27. DOI: 10.1210/me.2003-0441. View

16.

Broussard A, Florwick A, Desbiens C, Nischan N, Robertson C, Guan Z . Human UDP-galactose 4'-epimerase (GALE) is required for cell-surface glycome structure and function. J Biol Chem. 2019; 295(5):1225-1239. PMC: 6996900. DOI: 10.1074/jbc.RA119.009271. View

17.

Canellada A, Alvarez I, Berod L, Gentile T . Estrogen and progesterone regulate the IL-6 signal transduction pathway in antibody secreting cells. J Steroid Biochem Mol Biol. 2008; 111(3-5):255-61. DOI: 10.1016/j.jsbmb.2008.06.009. View

18.

Catera M, Borelli V, Malagolini N, Chiricolo M, Venturi G, Reis C . Identification of novel plasma glycosylation-associated markers of aging. Oncotarget. 2016; 7(7):7455-68. PMC: 4884931. DOI: 10.18632/oncotarget.7059. View

19.

Cheng H, Tirosh I, de Haan N, Stockmann H, Adamczyk B, McManus C . IgG Fc glycosylation as an axis of humoral immunity in childhood. J Allergy Clin Immunol. 2019; 145(2):710-713.e9. PMC: 7010538. DOI: 10.1016/j.jaci.2019.10.012. View

20.

Cymer F, Schlothauer T, Knaupp A, Beck H . Evaluation of an FcRn affinity chromatographic method for IgG1-type antibodies and evaluation of IgG variants. Bioanalysis. 2017; 9(17):1305-1317. DOI: 10.4155/bio-2017-0109. View