Immunoglobulin G glycome composition in transition from premenopause to postmenopause
Helena Deriš,
Domagoj Kifer,
Ana Cindrić,
Tea Petrović,
Ana Cvetko,
Irena Trbojević-Akmačić,
Ivana Kolčić,
Ozren Polašek,
Louise Newson,
Tim Spector,
Cristina Menni,
Gordan Lauc
Affiliations
Helena Deriš
Genos Glycoscience Research Laboratory, Zagreb 10000, Croatia
Domagoj Kifer
Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb 10000, Croatia
Ana Cindrić
Genos Glycoscience Research Laboratory, Zagreb 10000, Croatia
Tea Petrović
Genos Glycoscience Research Laboratory, Zagreb 10000, Croatia
Ana Cvetko
Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb 10000, Croatia
Irena Trbojević-Akmačić
Genos Glycoscience Research Laboratory, Zagreb 10000, Croatia
Ivana Kolčić
University of Split School of Medicine, Split 21000, Croatia; Algebra University College, Zagreb 10000, Croatia
Ozren Polašek
University of Split School of Medicine, Split 21000, Croatia; Algebra University College, Zagreb 10000, Croatia
Louise Newson
Newson Health Menopause & Wellbeing Centre, Church Street, Stratford-Upon-Avon CV37 6HB, UK
Tim Spector
Department of Twin Research and Genetic Epidemiology, King’s College London, Westminster Bridge Road, SE17EH London, UK
Cristina Menni
Department of Twin Research and Genetic Epidemiology, King’s College London, Westminster Bridge Road, SE17EH London, UK
Gordan Lauc
Genos Glycoscience Research Laboratory, Zagreb 10000, Croatia; Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb 10000, Croatia; Corresponding author
Summary: Gonadal 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.
