Periodic Changes in the N-Glycosylation of Immunoglobulin G During the Menstrual Cycle
Julija Jurić,
Hongli Peng,
Manshu Song,
Frano Vučković,
Jelena Šimunović,
Irena Trbojević-Akmačić,
Youxin Wang,
Jiaonan Liu,
Qing Gao,
Hao Wang,
Qiaoyun Chu,
Marija Pezer,
Wei Wang,
Gordan Lauc
Affiliations
Julija Jurić
Genos Glycoscience Research Laboratory, Zagreb 10000, Croatia
Hongli Peng
Hospital of Traditional Chinese Medicine, Fengtai District, Beijing 100076, China; Beijing Municipal Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China
Manshu Song
Beijing Municipal Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China; Centre for Precision Health, Edith Cowan University, Perth, WA 6027, Australia
Frano Vučković
Genos Glycoscience Research Laboratory, Zagreb 10000, Croatia
Jelena Šimunović
Genos Glycoscience Research Laboratory, Zagreb 10000, Croatia
Irena Trbojević-Akmačić
Genos Glycoscience Research Laboratory, Zagreb 10000, Croatia
Youxin Wang
Beijing Municipal Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China; Centre for Precision Health, Edith Cowan University, Perth, WA 6027, Australia
Jiaonan Liu
Hospital of Traditional Chinese Medicine, Fengtai District, Beijing 100076, China; Beijing Municipal Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China
Qing Gao
Beijing Municipal Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China
Hao Wang
Beijing Municipal Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China; Centre for Precision Health, Edith Cowan University, Perth, WA 6027, Australia
Qiaoyun Chu
School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
Marija Pezer
Genos Glycoscience Research Laboratory, Zagreb 10000, Croatia
Wei Wang
Beijing Municipal Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China; Centre for Precision Health, Edith Cowan University, Perth, WA 6027, Australia; Corresponding authors.
Gordan Lauc
Genos Glycoscience Research Laboratory, Zagreb 10000, Croatia; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy and Biochemistry at University of Zagreb, Zagreb 10000, Croatia; Corresponding authors.
Immunoglobulin G (IgG) is the most abundant plasma glycoprotein and a prominent humoral immune mediator. Glycan composition affects the affinity of IgG to ligands and consequent immune responses. The modification of IgG N-glycosylation is considered to be one of the various mechanisms by which sex hormones modulate the immune system. Although the menstrual cycle is the central sex hormone-related physiological process in most women of reproductive age, IgG N-glycosylation dynamics during the menstrual cycle have not yet been investigated. To fill this gap, we profiled the plasma IgG N-glycans of 70 healthy premenopausal women at 12 time points during their menstrual cycles (every 7 days for 3 months) using hydrophilic interaction ultra-performance liquid chromatography (HILIC-UPLC). We observed cyclic periodic changes in the N-glycosylation of IgG in association with the menstrual cycle phase and sex hormone concentration in plasma. On the integrated cohort level, the modeled average menstrual cycle effect on the abundance of IgG N-glycosylation traits was low for each trait, with the highest being 1.1% for agalactosylated N-glycans. However, intrapersonal changes were relatively high in some cases; for example, the largest difference between the minimum and maximum values during the menstrual cycle was up to 21% for sialylated N-glycans. Across all measurements, the menstrual cycle phase could explain up to 0.72% of the variation in the abundance of a single IgG glycosylation trait of monogalactosylation. In contrast, up to 99% of the variation in the abundance of digalactosylation could be attributed to interpersonal differences in IgG N-glycosylation. In conclusion, the average extent of changes in the IgG N-glycopattern that occur during the menstrual cycle is small; thus, the IgG N-glycoprofiling of women in large sample-size studies can be performed regardless of menstrual cycle phase.
