Immunoglobulin G glycome composition in transition from pre-menopause to menopause

Abstract

Background Glycosylation of immunoglobulin G (IgG) is an important regulator of the immune system and its changes are believed to be a significant contributor to inflammaging. 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. Methods IgG was isolated from 5,354 plasma samples collected from 1,940 females and 113 males at multiple time points. IgG glycans were released, labelled with a fluorescent dye and analysed by ultra-high-performance liquid chromatography. Mixed modelling was used to determine average levels of individual IgG glycans in pre-menopausal women, menopausal women, and men. Findings 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 significant higher 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 - -0.037, p<0.001), and monosialylated glycans (-0.029/yr; 95%CI = -0.034 - -0.024, p<0.001), compared to premenopausal women. Interpretation 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. IgG glycome changes considerably during perimenopause and may aid the diagnosis of perimenopause. Funding Croatian National Centre of Excellence in Personalised Healthcare, ESI Funds grant for the Centre of Competences in Molecular Diagnostics, the Wellcome Trust and the Medical Research Council (MRC)/British Heart Foundation (BHF).