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Estrogens regulate glycosylation of IgG in women and men
Altan Ercan, … , Joel S. Finkelstein, Peter A. Nigrovic
Altan Ercan, … , Joel S. Finkelstein, Peter A. Nigrovic
Published February 23, 2017
Citation Information: JCI Insight. 2017;2(4):e89703. https://doi.org/10.1172/jci.insight.89703.
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Categories: Research Article Endocrinology Immunology

Estrogens regulate glycosylation of IgG in women and men

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Abstract

The immunologic potency of IgG is modulated by glycosylation, but mechanisms regulating this process are undefined. A role for sex hormones is suggested by differences in IgG glycans between women and men, most prominently with respect to galactose. We therefore assessed IgG galactosylation in 713 healthy adults from 2 cohorts as well as in 159 subjects from 4 randomized controlled studies of endocrine manipulation: postmenopausal women receiving conjugated estrogens, raloxifene, or placebo; premenopausal women deprived of gonadal hormones with leuprolide and treated with estradiol or placebo; men deprived of gonadal hormones with goserelin and given testosterone or placebo; and men deprived of gonadal hormones with goserelin and given testosterone or placebo together with anastrozole to block conversion of testosterone to estradiol. Menopause was associated with an increase in agalactosylated IgG glycans, particularly in the most abundant fucosylated nonbisected (G0F) glycoform. Conjugated estrogens and raloxifene reduced G0F glycans in postmenopausal women, while in premenopausal women leuprolide increased G0F glycans in a manner reversed by estradiol. Among men, goserelin increased G0F glycans, an effect blocked by testosterone through conversion to estradiol. These results establish estrogens as an in vivo modulator of IgG galactosylation in both women and men, defining a pathway by which sex modulates immunity.

Authors

Altan Ercan, Wendy M. Kohrt, Jing Cui, Kevin D. Deane, Marija Pezer, Elaine W. Yu, Jonathan S. Hausmann, Harry Campbell, Ursula B. Kaiser, Pauline M. Rudd, Gordan Lauc, James F. Wilson, Joel S. Finkelstein, Peter A. Nigrovic

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Figure 1

Schematic representation of IgG Fc glycans.

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Schematic representation of IgG Fc glycans.
The Fc region of IgG contain...
The Fc region of IgG contains two glycans, one per heavy chain, attached to the single conserved glycosylation site at asparagine (Asn) 297. The most complex glycan, presented at the top, contains 13 monosaccharide units, including 2 galactoses (i.e., G2), a bisecting N-acetylglucosamine, a core fucose attached to core N-acetylglucosamine, and terminal sialic acids. Other IgG Fc glycans are similar in overall structure but lack one or more monosaccharide. These smaller forms include the three presented below: G0F (no galactoses, no bisecting N-acetylglucosamine, with core fucose), G0FB (same as G0F, with a bisecting N-acetylglucosamine), and G1F (galactose attached to either the α1,6 or α1,3 arm).
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