Format

Send to

Choose Destination
JCI Insight. 2017 Feb 23;2(4):e89703. doi: 10.1172/jci.insight.89703.

Estrogens regulate glycosylation of IgG in women and men.

Author information

1
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA.; UtopicPharma LLC, Odessa, Florida, USA.
2
Division of Geriatrics and.
3
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA.
4
Division of Rheumatology, University of Colorado Denver School of Medicine, Aurora, Colorado, USA.
5
Genos Glycoscience Research Laboratory, Zagreb, Croatia.
6
Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
7
Division of Immunology, Boston Children's Hospital, Boston, Massachusetts, USA.; Division of Rheumatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
8
Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland.
9
Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, Massachusetts, USA.
10
National Institute for Bioprocessing Research and Training, University College Dublin, Dublin, Ireland.
11
Genos Glycoscience Research Laboratory, Zagreb, Croatia.; Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
12
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.
13
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Division of Immunology, Boston Children's Hospital, Boston, Massachusetts, USA.

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.

Conflict of interest statement

Conflict of interest: A. Ercan is the founder of UtopicPharma LLC. M. Pezer is an employee of the Genos Glycoscience Research Laboratory. E.W. Yu holds an investigator-initiated grant from Seres Therapeutics Inc. G. Lauc is the founder and chief executive officer of Genos and holds several glycobiology patents (PK20130568A, US20160103137, GB2361699 ). K.D. Deane holds investigator-initiated grants from Pfizer Inc. and Janssen Pharmaceuticals Inc. U.B. Kaiser has equity in Merck, GlycoMimetics, ImmunoGen, Blueprint Medicines, Agios, Express Scripts, Akebia, Amgen, Celgene, Hologic, Johnson & Johnson, Pfizer Inc., and Teva as well as spousal income from ImmunoGen, GlycoMimetics, Blueprint Medicines, Idera, aTyr, and Imara. J.S. Finkelstein holds an investigator-initiated grant from AbbVie Inc. P.A. Nigrovic receives salary support as a member of the steering committee of the Childhood Arthritis and Rheumatology Research Alliance; authorship royalties from UpToDate Inc. and the American Academy of Pediatrics; and holds investigator-initiated grants from Novartis Inc. and Sobi Inc.

Supplemental Content

Full text links

Icon for American Society for Clinical Investigation Icon for PubMed Central
Loading ...
Support Center