Estrogens regulate glycosylation of immunoglobulin G in women and men

The immunologic potency of immunoglobulin G 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 treated comparably 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 non-bisected (G0F) glycoform. Conjugated estrogens and raloxifene reduced G0F in postmenopausal women, while in premenopausal women leuprolide increased G0F in a manner reversed by estradiol. Among men, goserelin increased G0F, 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 new pathway by which sex modulates immunity.