title: Estrogens regulate glycosylation of IgG in women and men.
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.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA.|UtopicPharma LLC, Odessa, Florida, USA.
authors.forename: Altan
authors.initials: A
authors.lastname: Ercan
authors.affiliation: Division of Geriatrics and.
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Kohrt
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Cui
authors.affiliation: Division of Rheumatology, University of Colorado Denver School of Medicine, Aurora, Colorado, USA.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Deane
authors.affiliation: Genos Glycoscience Research Laboratory, Zagreb, Croatia.
authors.forename: Marija
authors.initials: M
authors.lastname: Pezer
authors.affiliation: Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Elaine W
authors.initials: EW
authors.lastname: Yu
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, Massachusetts, USA.|Division of Rheumatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Hausmann
authors.affiliation: Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland.
authors.forename: Harry
authors.initials: H
authors.lastname: Campbell
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Ursula B
authors.initials: UB
authors.lastname: Kaiser
authors.affiliation: National Institute for Bioprocessing Research and Training, University College Dublin, Dublin, Ireland.
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Rudd
authors.affiliation: Genos Glycoscience Research Laboratory, Zagreb, Croatia.|Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
authors.forename: Gordan
authors.initials: G
authors.lastname: Lauc
authors.affiliation: Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland.|MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, Scotland.
authors.forename: James F
authors.initials: JF
authors.lastname: Wilson
authors.affiliation: Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Finkelstein
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Division of Immunology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Nigrovic
mesh_terms: D000328:Adult; D000077384:Anastrozole / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology; D047072:Aromatase Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology; D005260:Female; D005300:Fertility Agents, Female / Q000494:pharmacology; D005690:Galactose / Q000378:metabolism*; D006031:Glycosylation / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D017273:Goserelin / Q000494:pharmacology; D064368:Healthy Volunteers; D006801:Humans; D007074:Immunoglobulin G / Q000187:drug effects / Q000378:metabolism*; D016729:Leuprolide / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011134:Polysaccharides / Q000378:metabolism*; D017698:Postmenopause; D017697:Premenopause; D020849:Raloxifene Hydrochloride / Q000494:pharmacology; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D012737:Sex Factors; D013739:Testosterone / Q000494:pharmacology
chemical_list: D000728:Androgens; D047072:Aromatase Inhibitors; D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D005300:Fertility Agents, Female; D007074:Immunoglobulin G; D011134:Polysaccharides; D020845:Selective Estrogen Receptor Modulators; D017273:Goserelin; D000077384:Anastrozole; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D016729:Leuprolide; D005690:Galactose