engleski

Immunoglobulin G glycome composition in transition from premenopause to postmenopause

Glycosylation of immunoglobulin G (IgG) is an important regulator of the immune system and its changes were shown to contribute to both inflammaging and cardiovascular disease risk. Each IgG molecule has an N-glycosylation site on each of its heavy chains that influences its structural stability, conformation and half-life, as well as effector functions. Gonadal hormones affect IgG glycome composition, suggesting that alterations in IgG glycosylation might be one of the molecular mechanisms behind increased disease risk in perimenopause. We used ultra-high-performance liquid chromatography to analyse IgG glycome composition in a unique collection of 5, 080 serum samples collected from 1, 940 females at multiple time points. Mixed modelling was used to determine average levels of individual IgG glycans in premenopausal and postmenopausal women. Large and statistically significant differences in IgG glycome composition were observed, mainly reflecting decreased galactosylation and sialylation of glycans in menopausal women. During perimenopause, women had a significantly higher rate of increase in agalactosylated structures and a decrease in digalactosylated and monosialylated glycans, compared to premenopausal women. 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. Furthermore, the increased pace of changes in the IgG glycome composition during perimenopause may aid the diagnosis of perimenopause. Early perimenopause diagnosis would enable timely interventions to ease the symptoms and decrease the risks of developing accompanying diseases.

IgG, glycosylation, menopause, perimenopause

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