Abstract
SummaryGonadal hormones affect immunoglobulin G (IgG) glycosylation, and the more proinflammatory IgG glycome composition might be one of the molecular mechanisms behind the increased proinflammatory phenotype in perimenopause. Using ultra-high-performance liquid chromatography, we analyzed IgG glycome composition in 5,080 samples from 1940 pre-, peri-, and postmenopausal women. Statistically significant decrease in galactosylation and sialylation was observed in postmenopausal women. Furthermore, during the transition from pre- to postmenopausal period, the rate of increase in agalactosylated structures (0.051/yr; 95%CI = 0.043–0.059, p < 0.001) and decrease in digalactosylated (−0.043/yr; 95%CI = −0.050 to −0.037, p < 0.001) and monosialylated glycans (−0.029/yr; 95%CI = −0.034 to −0.024, p < 0.001) were significantly higher than in either pre- or postmenopausal periods. The conversion to the more proinflammatory IgG glycome and the resulting decrease in the ability of IgG to suppress low-grade chronic inflammation may be an important molecular mechanism mediating the increased health risk in perimenopause and postmenopause.
Highlights
Glycosylation of immunoglobulin G (IgG) is an important regulator of the immune system (Martinic Kavur et al, 2021)
IgG glycome composition in premenopause and menopause IgG glycome composition was analyzed in multiple samples from 1,940 females and 113 males from the UK registry of adult twins
By analyzing IgG glycome in multiple samples from the same individuals, we have shown the association between the period of perimenopause and the extensive changes in the IgG glycome composition
Summary
Glycosylation of immunoglobulin G (IgG) is an important regulator of the immune system (Martinic Kavur et al, 2021). In addition to directly affecting the effector functions of IgG by promoting its binding to different Fc receptors (Nimmerjahn and Ravetch, 2008a), glycans attached to IgG have numerous other roles in the regulation of the immune system (Ipsen-Escobedo and Nimmerjahn, 2018; Seeling et al, 2017). One of the regulators of IgG glycosylation are sex hormones, and the association between estradiol and the IgG glycome composition was confirmed to be causal (Ercan et al, 2017). A recent randomized placebo-controlled clinical study demonstrated that the deprivation of gonadal hormones resulted in an increase of biological age measured by IgG glycans, which was completely prevented by estradiol supplementation (Juric et al, 2020)
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